Neuromodulation System and Method with Feedback Optimized Electrical Field Generation

ABSTRACT

A neuromodulation system and method with feedback optimized electrical field generation for stimulating target tissue of a patient to treat neurological and non-neurological conditions. The system generally includes implantable electrodes, implantable sensors, an implantable or external electrical signal generator, and an implantable or external controller. The controller controls the electrical signal generator to generate electrical noise stimulation signals that are delivered to the target tissue via the electrodes and that produce an optimized electric field having maximized voltage with low current density. The sensors produce temperature and impedance data for the target tissue and the controller automatically responds to values of the sensor data that indicate potential damage to the target tissue to reduce the strength of the electric field.

CROSS REFERENCE TO RELATED APPLICATIONS

The present application is a continuation of U.S. application Ser. No.17/111,950 filed on Dec. 4, 2020 which issues as U.S. Pat. No.11,065,450 on Jul. 20, 2021 (Docket No. SOIN-013), which is acontinuation of U.S. application Ser. No. 17/109,512 filed on Dec. 2,2020 now issued as U.S. Pat. No. 10,953,231 (Docket No. SOIN-011), whichis a continuation of U.S. application Ser. No. 16/848,691 filed on Apr.14, 2020 now issued as U.S. Pat. No. 10,857,364 (Docket No. SOIN-005).Each of the aforementioned patent applications, and any applicationsrelated thereto, is herein incorporated by reference in their entirety.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

Not applicable to this application.

BACKGROUND Field

Example embodiments in general relate to a neuromodulation system andmethod with feedback optimized electrical field generation formodulating the activity of or stimulating neural tissue, non-neuraltissue, or a combination thereof as a therapeutic treatment for pain andother neurological and non-neurological conditions.

Related Art

Any discussion of the related art throughout the specification should inno way be considered as an admission that such related art is widelyknown or forms part of common general knowledge in the field.

A number of technologies and methods have been used to treatneurological and non-neurological conditions such as pain, incontinence,depression, obesity, headaches, and others. Both destructive andnon-destructive methods have been used to treat pain. Variousdestructive methods have been used to treat chronic pain indicationsincluding radiofrequency (RF) ablation, cryoablation, chemical ablation(phenols, Botox®), ultrasonography ablation and mechanical transection.However, destructive methods cause destruction of the portion of a nervein the treatment zone, which in turn causes an immediate loss offunctionality (e.g., motor, sensory, and proprioception) and may lead tolong-term atrophy, neuropathy and more pain. Consequently, destructivemethods are typically treatments of last resort, and should be usedsparingly.

Various non-destructive methods also have been used to treat painincluding the use of prescription pain medications (opioids), localanesthetic injections, topical cocktails consisting of steroids andother anti-inflammatory agents, continuous infusion of localanesthetics, and electrical stimulation. Each method presents a uniqueset of challenges that can compromise treatment efficacy and/orusability.

For example, non-destructive methods using drugs, typically includingopioids, can put patients at risk for unwanted side effects such asconstipation, nausea, emesis, and ileus, and can ultimately result inaddiction and even death. Non-destructive methods using injections oflocal anesthetic and/or cocktails typically have a short effectiveduration which may last only a period of hours, and may becomeineffective over time. Such methods thus typically require continued,daily maintenance. Continuous infusion of anesthetics generally requiresan external device be tethered to the patient for long-term treatment,often over a period of days. Daily device maintenance is thus a burdenfor patients and is often an unwanted reminder that they have pain. Theuse of local anesthetics and long-lasting locals (e.g., Exparel®) mayalso cause nerve toxicity, vascular toxicity and allergic reactions.Further, these agents are not immediately reversible, titratable orselective to the type of nerve activity that they block (e.g., pain vs.motor).

Electrical stimulation technologies have been used to mitigate bothacute (e.g., post-surgical) and chronic pain types. Unlikepharmaceutical interventions, electrical stimulation technologies arereversible, non-addictive, and can be selective depending on theirstimulation paradigm and treatment site. Electrical stimulation can bedelivered to various parts of the central and peripheral nervoussystems, including the sensory receptors in the brain, spinal cord,skin, and various peripheral nerves. Moreover, electrical stimulatorscan be configured to provide treatment in a transcutaneous,percutaneous, and/or implantable fashion.

Two electrical stimulation paradigms have been primarily used for thetreatment of pain, both employing electrical signals with periodicwaveforms. Traditional stimulation uses relatively low frequency (e.g.,<1500 Hz) electrical signals to produce paresthesia, which can to someextent mask pain with a sensation of tingling or numbness. Sub-sensoryparesthesia stimulation, such as employed in the HF10® technology byNevro Corp., uses relatively higher frequency (e.g, 10 KHz range)electrical signals to at least partially block the transmission of nervesignals to the brain. See, e.g., International Patent App. Pub. No. WO2009/061813 A1.

Unlike local anesthetics, neither of these electrical stimulation typescompletely eliminates painful sensations. Traditional stimulation onlyattenuates painful sensations, and simultaneously elicits electricalparesthesia (i.e., a buzzing, tingling, or vibration sensation), whichcovers the receptive field of the stimulated nerve. Sub-sensoryparesthesia stimulation does not elicit electrical paresthesia but isstill effective at attenuating painful sensations. Further, despite thepromise of electrical stimulation, its therapeutic efficacy can reduceafter a few years of use. This phenomenon is known as neurologicaltolerance and is the major reason for the removal of implantedstimulators from patients. Still further, the use of periodic electricalstimulation signals with relatively low frequency, e.g., less than about100 KHz, deliver relatively short-term therapeutic effects. Thus, whilethe therapeutic effects from electrical stimulation using such signalstypically begin to be felt within minutes-to-hours after the stimulationbegins, they tend to only last for a relatively short period of time,e.g., a few hours, after the therapy has been discontinued. Because thetherapeutic effects tend to be short-lived, continuous and/or frequentstimulation sessions are generally required to provide therapeuticeffects that are felt for longer periods of time. This, in turn,typically results in the need for on-going device maintenance (e.g.,daily battery charging) which is burdensome and inconvenient.

Electrical stimulation has also been used to treat other neurologicaland non-neurological conditions such as incontinence, obesity andothers. For example, electrical stimulation signals have been applied tothe nerves, e.g., sacral and posterior tibial nerves, and muscles, e.g.,pelvic muscles, associated with the bladder and with urination as atreatment for incontinence. Electrical stimulation of the intestinaltract has been used as a treatment for gastrointestinal motilitydisorders and obesity. Electrical stimulation signals also have beenapplied to the nerves and muscles of the stomach in order to inhibit ormitigate the sensation of hunger and/or to modulate gastric motorfunction as a treatment for obesity and to help control chronic nauseaand vomiting associated with gastroparesis as a result of diabetes.

Recently, International Patent App. Pub No. WO 2018/136354 A1 (“the '354Application”) has disclosed to employ electrical signals exhibitingstatistically random waveforms, i.e., noise, to provide stimulation ormodulation of neural tissue, non-neural tissue, or a combination thereofto treat pain and certain other neurological disorders. According to the'354 Application the electrical noise signals can be tuned and can thusprovide better patient outcomes than conventional periodic electricalsignals. The '354 Application discloses to tune or adjust the electricalnoise signals by delivering the noise signals to a patient and thentuning or adjusting the signals based on feedback provided by thepatient as to what the patient is feeling. However, if the patient isunable to provide accurate and timely feedback, the noise signals cannotbe accurately or properly tuned, and the resulting effects will betherapeutically sub-optimal and possibly even adverse. The patient couldeven suffer discomfort or tissue damage as a result.

The use of tunable statistically random electrical noise signals tomodulate or stimulate neural tissue, non-neural tissue or a combinationof both as described in the '354 Application can provide improvedtherapeutic results compared to the use of conventional periodicelectrical signals. However, the present inventor has discovered thateven better and longer-lasting therapeutic results can be achieved byoptimizing and maximizing the electric field produced in the targettissue. Optimizing and maximizing the electric field in the targettissue produces long-term plastic functional change in the tissue. As aresult, relatively shorter and less frequent treatments can providetherapeutic results that remain effective over relatively long periodsof time without the need to apply electrical signals to the targettissue continuously or repeatedly at short intervals. At the same time,the electric field must be optimized and maximized in a way that doesnot cause the patient discomfort or subject the target tissue topotential damage. Further, the optimized and maximized electric fieldmust be rapidly and automatically controlled in response to changes inphysical parameters associated with the target tissue to avoid causingpatient discomfort or tissue damage.

There is thus a need for a neuromodulation system and method thataddresses various deficiencies and drawbacks of conventional treatmentapparatuses and methods. More specifically, there is a need for such asystem and method that uses electrical noise signals to modulate orstimulate target neural tissue, non-neural tissue, or a combinationthereof to effectively treat neurological and non-neurologicalconditions including but not limited to acute and chronic pain types,Parkinson's disease, seizures, depression, bowl/bladder incontinence,obesity (to induce less appetite), etc. There is a need for such asystem and method that is non-destructive to the tissue treated, thatpreserves all other neurological functions of the tissue such as touch,motors, proprioception, etc., and that provides effective therapeuticresults without inducing tolerance. There is a need for such a systemand method that can apply less frequent and shorter treatments andproduce therapeutic results that are effective over relatively longperiods of time, thus also reducing the need for device maintenance,e.g., battery re-charging. There is a need for such a system and methodthat can optimize and maximize the electrical field produced in thetarget tissue to achieve the foregoing therapeutic effects while rapidlyand automatically controlling the electric field in response to changesin physical parameters associated with the tissue to avoid causingpatient discomfort or tissue damage.

SUMMARY

Example embodiments are directed to a neuromodulation system and methodwith feedback optimized electrical field generation to provide atherapeutic effect to target tissue of a patient. The target tissue canbe neurological tissue, non-neurological tissue, or a combination ofboth. The target tissue can be tissue that is within or adjacent totissue of the patient's central, peripheral, or autonomic nervous systemincluding the brain, spinal cord, dorsal root ganglions, sympatheticchain ganglions, cranial nerves, parasympathetic nerves, and peripheralnerves, among others. The target tissue can be neurological ornon-neurological tissue associated with other organs including thestomach, bladder, and intestines. The therapeutic effect comprises aplastic long-term functional change in the target tissue to lessen oreliminate a pathophysiologic disease or syndrome. The therapeutic effectcan treat a plurality of neurological and non-neurological conditionsincluding chronic and acute pain, autonomic disorder, sensory disorder,motor disorder, movement disorders, and cognitive disorder, obesity,psychiatric conditions, seizure disorders, and incontinence amongothers.

The neuromodulation system and method with feedback optimized electricalfield generation generally includes an implantable electrode, animplantable sensor, an electrical signal generator coupled to theimplantable electrode, and a controller coupled to the implantablesensor and to the electrical signal generator.

The electrical signal generator may be external or implantable in apatient. The electrical signal generator is adapted to generate anelectrical noise stimulation signal for stimulating or modulating targettissue of the patient comprising neurological tissue, non-neurologicaltissue, or a combination of both.

The implantable electrode may comprise one or a plurality of electrodesand is implantable in or near the target tissue. The electrode receivesthe electrical noise stimulation signal and delivers it to the targettissue to produce an electric field in the target tissue.

The implantable sensor may comprise a single sensor or a plurality ofsensors. The sensor or sensors may be incorporated with the electrode orelectrodes and may be separately implantable in or near the targettissue. The sensor or sensors generate data indicative of a physicalparameter associated with the target tissue. In one aspect, the sensorcomprises a temperature sensor and the physical parameter of the targettissue comprises temperature. In another aspect, the sensor comprises animpedance sensor and the physical parameter of the target tissuecomprises impedance.

The controller may be external or implantable in the patient. Thecontroller is configured to receive the sensor data and in response toautomatically control the electrical signal generator to generate theelectrical noise stimulation signal in a way to optimize and maximizethe electric field to produce an optimal therapeutic effect but with theelectric field not resulting in sensor data that indicates a value ofthe physical parameter of the target tissue that is associated withpotential damage to the target tissue.

Generally, the controller is configured to control the electrical signalgenerator to optimize and maximize the electric field by generating andapplying an electrical noise stimulation signal that maximizes thevoltage component of the electric field while maintaining a level ofcurrent density and flow to the target tissue so that the sensor datadoes not indicate a value of the physical parameter of the target tissueassociated with potential damage to the target tissue. In one aspect,the electrical noise stimulation signal can have a peak voltage level inthe range of about 5V to about 200V and current flow can be maintainedin a range of about 10 mA to about 300 mA or less. The electrical noisestimulation signal can have a frequency spectrum in the range of about50 Hz., and more preferably about 100 Hz., to about 750 KHz.

In one aspect, the electrical signal generator is adapted to generatethe electrical noise stimulation signal in a frequency band having acenter frequency corresponding to a peak value of impedance, and thecontroller is configured to control the electrical signal generator tooptimize and maximize the electric field by adjusting the centerfrequency. In one aspect, the electrical signal generator is adapted togenerate the electrical noise stimulation signal in a plurality ofselectable frequency bands corresponding to a plurality of peak valuesof impedance, and the controller is configured to control the electricalsignal generator to optimize and maximize the electric field byselecting one of the frequency bands. In one aspect, the systemcomprises a plurality of selectable combinations of implantableelectrodes, the electrical signal generator is adapted to generate theelectrical noise stimulation signal so it is received by a selectedcombination of the implantable electrodes, and the controller isconfigured to control the electrical signal generator to optimize andmaximize the electric field by selecting the combination of implantableelectrodes that is to receive the electrical noise stimulation signal.

The controller is configured to automatically respond to sensor dataindicating a value of the physical parameter associated with potentialdamage to the target tissue to automatically take an action to reducethe strength of the electric field. In one aspect, the action to reducethe strength of the electric field comprises an action to reduce thecurrent density and flow to the target tissue. In one aspect, the valueof the physical parameter that is associated with potential damage tothe target tissue may be a specific value of high temperature, e.g., 42°C., or a temperature range. In another aspect, the value of the physicalparameter that is associated with potential damage to the target tissuemay be a specific value of low impedance or an impedance range.

There has thus been outlined, rather broadly, some of the embodiments ofthe neuromodulation system and method with feedback optimized electricalfield generation in order that the detailed description thereof may bebetter understood, and in order that the present contribution to the artmay be better appreciated. There are additional embodiments of theneuromodulation system and method with feedback optimized electricalfield generation that will be described hereinafter and that will formthe subject matter of the claims appended hereto. In this respect,before explaining at least one embodiment of the neuromodulation systemand method with feedback optimized electrical field generation indetail, it is to be understood that the neuromodulation system andmethod with feedback optimized electrical field generation is notlimited in its application to the details of construction or to thearrangements of the components set forth in the following description orillustrated in the drawings. The neuromodulation system and method withfeedback optimized electrical field generation is capable of otherembodiments and of being practiced and carried out in various ways.Also, it is to be understood that the phraseology and terminologyemployed herein are for the purpose of the description and should not beregarded as limiting.

BRIEF DESCRIPTION OF THE DRAWINGS

Example embodiments of the neuromodulation system and method withfeedback optimized electrical field generation will become more fullyunderstood from the detailed description given herein below and theaccompanying drawings, wherein like elements are represented by likereference characters, which are given by way of illustration only andthus are not limitative of the example embodiments herein.

FIG. 1 is a schematic view of a neuromodulation system and method withfeedback optimized electrical field generation in connection withelectrical noise stimulation of target neural tissue associated with acentral nervous system, more specifically target neural tissue in abrain, in accordance with an example embodiment.

FIG. 2 is an enlargement of the portion of FIG. 1 contained withindashed lines.

FIG. 3 is a schematic view of a neuromodulation system and method withfeedback optimized electrical field generation in connection withelectrical noise stimulation of target neural tissue associated with acentral nervous system, more specifically target neural tissue in abrain, in accordance with another example embodiment.

FIG. 4 is a schematic view of a neuromodulation system and method withfeedback optimized electrical field generation in connection withelectrical noise stimulation of target neural tissue associated with acentral nervous system, more specifically target neural tissue of aspinal cord, in accordance with an example embodiment.

FIG. 5 is an enlargement of the portion of FIG. 4 contained withindashed lines.

FIG. 6 is a schematic view of a neuromodulation system and method withfeedback optimized electrical field generation in connection withelectrical noise stimulation of target neural tissue associated with aperipheral nervous system, more specifically target neural tissue of aperipheral nerve, in accordance with an example embodiment.

FIG. 7 is a schematic view of a neuromodulation system and method withfeedback optimized electrical field generation in connection withelectrical noise stimulation of target non-neural tissue associated witha gastrointestinal tract, more specifically target non-neural tissue ofa stomach, in accordance with an example embodiment.

FIG. 8 is an enlargement of the portion of FIG. 7 contained withindashed lines.

FIG. 9 is a schematic view of a neuromodulation system and method withfeedback optimized electrical field generation in connection withelectrical noise stimulation of target neural tissue associated with aperipheral nervous system, more specifically target neural tissue of asacral nerve, in accordance with an example embodiment.

FIG. 10 is a block diagram illustrating the interconnections andcommunications between the major components of a neuromodulation systemand method with feedback optimized electrical field generation inaccordance with an example embodiment.

FIG. 11 is a block diagram illustrating the interconnections andcommunications between the major components of an implantable internalcontroller and noise generator of a neuromodulation system and methodwith feedback optimized electrical field generation in accordance withan example embodiment.

FIG. 12 is a block diagram illustrating the interconnections andcommunications between an implantable internal controller and anexternal controller of a neuromodulation system and method with feedbackoptimized electrical field generation in accordance with an exampleembodiment in connection with an external telecommunications network.

FIG. 13 is a graph illustrating the amplitude with respect to time of anelectrical noise stimulation signal of an implantable internalcontroller and noise generator of a neuromodulation system and methodwith feedback optimized electrical field generation in accordance withan example embodiment.

FIG. 14 is a graph illustrating the power spectrum with respect tofrequency of an electrical noise stimulation signal of an implantableinternal controller and noise generator of a neuromodulation system andmethod with feedback optimized electrical field generation in accordancewith an example embodiment.

FIG. 15A is a graph illustrating an impedance amplitude spectrum withrespect to frequency in response to application of an electrical noisestimulation signal of an implantable internal controller and noisegenerator of a neuromodulation system and method with feedback optimizedelectrical field generation in accordance with an example embodiment.

FIG. 15B is a graph illustrating another impedance amplitude spectrumwith respect to frequency in response to application of an electricalnoise stimulation signal of an implantable internal controller and noisegenerator of a neuromodulation system and method with feedback optimizedelectrical field generation in accordance with an example embodiment.

FIG. 15C is a graph illustrating yet another impedance amplitudespectrum with respect to frequency in response to application of anelectrical noise stimulation signal of an implantable internalcontroller and noise generator of a neuromodulation system and methodwith feedback optimized electrical field generation in accordance withan example embodiment.

FIG. 16 is a graph illustrating impedance amplitude with respect to timein response to application of an electrical noise stimulation signal ofan implantable internal controller and noise generator of aneuromodulation system and method with feedback optimized electricalfield generation in accordance with an example embodiment.

FIG. 17 is a graph illustrating temperature with respect to time inresponse to application of an electrical noise stimulation signal of animplantable internal controller and noise generator of a neuromodulationsystem and method with feedback optimized electrical field generation inaccordance with an example embodiment.

FIG. 18A is a partial perspective schematic view illustrating aselection of electrodes of a multi-electrode lead for application totissue of an electrical noise stimulation signal of an implantableinternal controller and noise generator of a neuromodulation system andmethod with feedback optimized electrical field generation in accordancewith an example embodiment.

FIG. 18B is a partial perspective schematic view illustrating anotherselection of electrodes of a multi-electrode lead for application totissue of an electrical noise stimulation signal of an implantableinternal controller and noise generator of a neuromodulation system andmethod with feedback optimized electrical field generation in accordancewith an example embodiment.

FIG. 18C is a partial perspective schematic view illustrating yetanother selection of electrodes of a multi-electrode lead forapplication to tissue of an electrical noise stimulation signal of animplantable internal controller and noise generator of a neuromodulationsystem and method with feedback optimized electrical field generation inaccordance with an example embodiment.

FIG. 18D is a partial perspective view graphically illustrating stillanother selection of electrodes of a multi-electrode lead forapplication to tissue of an electrical noise stimulation signal of animplantable internal controller and noise generator of a neuromodulationsystem and method with feedback optimized electrical field generation inaccordance with an example embodiment.

FIG. 19A is a partial perspective view graphically illustrating aselection of electrodes of a pair of percutaneous leads for applicationto tissue of an electrical noise stimulation signal of an implantableinternal controller and noise generator of a neuromodulation system andmethod with feedback optimized electrical field generation in accordancewith an example embodiment.

FIG. 19B is a partial perspective view graphically illustrating anotherselection of electrodes of a pair of percutaneous leads for applicationto tissue of an electrical noise stimulation signal of an implantableinternal controller and noise generator of a neuromodulation system andmethod with feedback optimized electrical field generation in accordancewith an example embodiment.

FIG. 19C is a partial perspective view graphically illustrating aselection of electrodes of a single percutaneous lead for application totissue of an electrical noise stimulation signal of an implantableinternal controller and noise generator of a neuromodulation system andmethod with feedback optimized electrical field generation in accordancewith an example embodiment.

DETAILED DESCRIPTION A. Overview.

Example embodiments of a neuromodulation system and method with feedbackoptimized electrical field generation 10 (referred to herein asneuromodulation system 10) provide effective and long-lastingtherapeutic results by delivering electrical noise stimulation signalsto target tissue 12 of a patient 14 in such a way as to optimize andmaximize the electric field in the target tissue 12 while preventingdamage to the target tissue 12 and discomfort to the patient 14. Byoptimizing and maximizing the electric field in the target tissue 12,the system is able to produce long-term plastic functional change in thetarget tissue 12 with treatments that are of relatively short duration.The treatments produce effective therapeutic results that are relativelylong-lasting.

The example embodiments of the neuromodulation system 10 optimize andmaximize the electric field in a way that maximizes the voltagecomponent of the electric field while maintaining a relatively low levelof current density and flow in the target tissue 12, thereby helping toprevent potential damage to the target tissue 12 and patient discomfortdue to heating effects. The example embodiments of the neuromodulationsystem 10 also rapidly and automatically respond to sensed values ofphysical parameters, e.g., temperature and impedance, that areassociated with the target tissue 12 that indicate potential damage tothe target tissue 12 by controlling the electric field to reduce itsintensity, including reducing current density and flow, to preventdamage to the target tissue 12 and patient 14 discomfort.

The example neuromodulation system 10 generally includes one or moreimplantable electrodes 30, one or more implantable sensors S1, S2, anelectrical signal generator 40 and a controller 50. The electricalsignal generator 40 and the controller 50 are preferably enclosed withinan implantable enclosure 16 that is adapted to be implanted in thepatient 14.

The electrodes 30 and the sensors S1, S2 are implantable in, on, oraround the target tissue 12 of the patient 14 to be treated. Theelectrical signal generator 40 is coupled to the implantable electrodes30 and the controller 50 is coupled to the implantable sensors S1, S2and to the electrical signal generator 40. The controller 50 is adaptedand configured to control the electrical signal generator 40 to generateand deliver electrical noise stimulation signals to the target tissue 12of the patient 14 via the electrodes 30. The electrical noisestimulation signals produce an electric field in the target tissue 12that is optimized and maximized by maximizing the voltage componentwhile maintaining the current density and flow at a relatively lowvalue. Optimizing and maximizing the electric field in this way resultsin long-term plastic functional change in the target tissue 12 withoutcausing damage to the target tissue 12 or discomfort to the patient 14due to heating effects.

The sensors S1, S2 are adapted to produce sensor data comprising valuesof physical parameters, e.g., temperature and impedance, of the targettissue 12 as the electrical noise stimulation signals are applied to thetarget tissue 12. The controller 50 is adapted and configured to receiveand use the sensor data to optimize and maximize the electric field fortreatment. The controller 50 also is adapted and configured to rapidlyand automatically respond to values of the sensor data that indicatepotential damage to the target tissue 12 to control the electricalsignal generator 40 to control the electric field in the target tissue12 by reducing the intensity of the electric field, including thecurrent density and flow.

A number of approaches for controlling the electric field to optimizeand maximize its strength and to reduce its strength are disclosed. Oneapproach includes limiting the time duration of the dose of electricalnoise stimulation signals. Another approach includes generating anddelivering the electrical noise stimulation signals in a relativelynarrow frequency band with a center frequency corresponding to a peakvalue of impedance and varying or adjusting the center frequency.Another approach includes generating and delivering the electrical noisestimulation signals in a plurality of relatively narrow frequency bandswith center frequencies corresponding to plurality of different peakimpedance values and selecting a frequency band with a desired value ofpeak impedance. Another approach includes selecting from among differentelectrodes 30 or combinations of electrodes 30 with different spacingand orientation in relation to the target tissue 12 and thus differentcorresponding impedance values to deliver the electrical noisestimulation signals.

B. System in General.

FIGS. 1-10 illustrate generally an example neuromodulation system 10that generates and delivers electrical noise stimulation signals totarget tissue 12 of a patient 14 in a way that optimizes and maximizesthe electric field in the target tissue 12 to provide effectivelong-lasting therapeutic results to the patient 14 by producinglong-term plastic functional change in the target tissue 12, and thatautomatically responds to feedback from sensors S1, S2 to control theelectric field and help prevent patient discomfort and potential tissuedamage.

In general, the example neuromodulation system 10 comprises one or moreimplantable electrodes 30, one or more implantable sensors S1, S2, anelectrical signal generator 40 electrically coupled to the implantableelectrodes 30, and a controller 50 electrically coupled to theimplantable sensors S1, S2 and to the electrical signal generator 40.The electrical signal generator 40 and the controller 50 may also beimplantable and may be enclosed within a suitable implantable enclosure16 within a patient 14. Suitable electrical leads 18 may electricallycouple the electrical signal generator 40 and the electrodes 30. Theimplantable enclosure 16 may be provided with lead connection ports 19for that purpose. Alternatively, as illustrated in FIG. 6, theelectrical signal generator 40 may be external to the patient 14 and theelectrical signal generator 40 and electrodes 30 may be wirelesslycoupled, for example electromagnetically via an antenna, inductively viaan inductive coil, or by any other suitable wireless arrangement.

As illustrated in FIG. 10, the neuromodulation system 10 also caninclude an internal power source 52 to provide power for the controller50 and the electrical signal generator 40, a separate externalcontroller 60, a user interface 62, and an external power source 64. Theexternal controller 60, if used, can be coupled to the controller 50directly or within the implantable enclosure 16 by a percutaneouselectrical lead 65 or wirelessly in any suitable manner including thoseidentified above.

The leads 18 with electrode or electrodes 30 may be implanted in or nearthe target tissue 12 of the patient 14 to be treated. In someapplications, the electrodes 30 also can be placed on or just under theskin of a patient at or near the target tissue 12. The sensors S1 and S2also may be implanted in or near the target tissue 12 and may be locatedcoincident with or near the electrodes 30.

As illustrated in FIGS. 1-3, in an example embodiment of theneuromodulation system 10 the target tissue 12 may comprise neuraltissue of the central nervous system of the patient 14 in, on or aroundthe patient's brain 22. For example for deep brain stimulation such asmay be used to treat certain neurological conditions, the electrodes 30are implanted relatively deep within the brain tissue. The electrodes 30may be located near the distal ends of relatively rigid insulated wires31 that extend from the distal ends of leads 18 such as illustrated inFIG. 2 or may be located in segmented portions 32 near the distal endsof the leads 18 as illustrated in FIG. 3, or a combination of both. Theexample embodiment of the neuromodulation system 10 can be used tostimulate the neural tissue in, on and around the brain 22 to treatvarious neurological conditions and diseases including but not limitedto chronic pain, acute pain, autonomic disorders, sensory disorders,motor disorders including tremors, tics, Tourette's syndrome, andParkinson's disease, cognitive disorders including Alzheimer's diseaseand dementia, depression, anxiety, psychiatric disorders includingschizophrenia, seizure disorders including epilepsy, narcolepsy,incontinence, and Meniere's disease.

In an example embodiment of the neuromodulation system 10 the targettissue 12 may comprise neural and non-neural tissue of the centralnervous system of the patient 14 on and around the patient's spinal cord24, including but not limited to neural and non-neural tissues in oraround the dorsal columns, dorsal roots, dorsal roots ganglion, andventral roots. As illustrated in FIGS. 4-5 for example, one or moreleads 18 with electrodes 30 near their distal ends can be inserted intothe epidural space between the bones of the spine and the spinal cordand advanced until one or more of the electrodes 30 are positioned on oradjacent to target neural and/or non-neural tissue in, on, or adjacentto the spinal cord.

The one or more electrodes 30 may be positioned at various locationslaterally relative to the spinal cord including, e.g., a dorsal(posterior) region, a dorsolateral region, a lateral region, and aventral (anterior) region, and may be positioned at various levels ofthe spine, e.g. S5-S1, L5-L1, T12-T1, and C8-C1, depending on thecondition to be treated. The example embodiment of the neuromodulationsystem 10 can be used to stimulate the neural tissue in, on and aroundthe spinal cord at various levels of the spine to treat various diseasesand syndromes. For example, a lead or plurality of leads 18 with one ormore electrodes 30 may be positioned within the epidural space on oradjacent to target neural tissue in, on, or around the spinal cord:

-   -   between T7 and T12 in the thoracic spine to treat spinal lumbar        pain disorders;    -   between T10-T11 in the thoracic spine to provide treatment for        chronic low back and leg pain;    -   between C2 and T1 in the cervical spine to treat spinal cervical        pain disorders;    -   between C2 and T8 in the spine to treat stable or unstable        angina;    -   between C2 and T8 in the spine to treat abdominal pain;    -   between T10-L5 in the spine to treat peripheral artery disease        of the lower limbs;    -   between C2 and T1 in the cervical spine to treat upper limb        ischemia. A lead or plurality of leads 18 with one or more        electrodes 30 may also be positioned within or near the dorsal        root ganglion to treat chronic or acute pain. Other conditions        that can be treated depending on the particular target tissue        stimulated and the spinal cord location and spine level of the        electrodes 30 include but are not limited to acute pain, failed        back surgery syndrome, complex regional pain syndrome,        peripheral vascular disease and chronic limb ischemia, angina        pain, diabetic pain, abdominal/visceral pain syndrome, brachial        plexitis, phantom limb pain, intractable pain secondary to        spinal cord injury, mediastinal pain, Raynaud's syndrome,        cervical neuritis, post herpetic neuralgia, vertigo, tinnitus,        hearing loss and inflammatory pain such as arthritis, irritable        bowel pain, osteoarthritis pain and fibromyalgia.

In an example embodiment of the neuromodulation system 10 the targettissue 12 may comprise neural and non-neural tissue of the peripheralnervous system of the patient 14 including tissues of the autonomicnervous system and the somatic nervous system. Target tissue 12 of theautonomic nervous system may comprise tissues of the sympathetic nervoussystem, e.g., the sympathetic chain ganglion and sympathetic nerves, andtissues of the parasympathetic nervous system, e.g., the parasympatheticnerves. Target tissue 12 of the somatic nervous system may comprise,e.g., the cranial nerves and the sacral nerves. The target tissue 12also may comprise neural and non-neural tissues of the major peripheralnerves including the tibial nerves, the sacral nerves, and the sciaticnerves, as well as any other peripheral nerves.

Depending on placement of the electrodes 30 in relation to target neuraland non-neural tissues of the sympathetic chain ganglion at variouslevels of the spine, the example embodiment of the neuromodulationsystem 10 can provide treatment for various conditions. For example, oneor more electrodes 30 may be positioned on or adjacent to target neuraltissue of the autonomic sympathetic chain anterior to the lumbar spinalcolumn at level L1 to stimulate or modulate the nerves of the celiacplexus that connect to the pancreas, gall bladder, intestines, liver,and stomach as a treatment for pain; level L3 to stimulate or modulatethe lumbar nerves that connect to the legs and feet as a treatment forpain; or level L5 to stimulate or modulate the hypogastric nerve thatconnects to the uterus, prostrate, bladder, rectum, and perineum as atreatment for incontinence and sexual dysfunction.

As further examples, a lead or plurality of leads 18 with one or moreelectrodes 30 may be positioned:

-   -   within the sacral nerve plexus or sacral foramen to treat        urinary or fecal incontinence;    -   near or around the lumbar sympathetic plexus to treat chronic or        acute pain of the limbs;    -   near or around the celiac sympathetic plexus to treat chronic or        acute pain of the abdomen;    -   near or around the hypogastric sympathetic plexus to treat        chronic or acute pain of the pelvic area;    -   near or around the stellate ganglion to treat pain of the upper        extremity;    -   near or around the vagus nerve to treat seizure disorders,        obesity, pain, or autonomic disorders;    -   near or around a peripheral nerve to treat acute pain, chronic        pain, fecal or urinary incontinence, seizure disorders, movement        disorders, obesity, spasticity, and to modulate other unpleasant        neurological conditions.

The electrodes 30 also may be positioned on or adjacent to other targetneural and non-neural tissues of the peripheral, autonomic, and somaticnervous systems associated with the eyes, lachrymal glands, salivaryglands, sweat glands, hair follicles and blood vessels of the head,neck, and arms, the heart and lungs, the stomach, duodenum, pancreas,liver, kidneys, colon, rectum, bladder, and genitalia, and the bloodvessels of the lower limbs and perineum, among others. The exampleembodiment of the neuromodulation system 10 can thus provide treatmentfor various diseases and syndromes including but not limited to complexregional pain syndrome, peripheral vascular disease and chronic limbischemia, angina pain, diabetic pain, abdominal/visceral pain syndrome,phantom limb pain, Raynaud's syndrome, hypertension, hypotension,headache and migraine, and inflammatory pain such as arthritis,irritable bowel pain, osteoarthritis pain and fibromyalgia. As furtherexamples, a lead or plurality of leads 18 with one or more electrodes 30may be positioned near or around somatic tissue, muscles, connectivetissue, or non-neural tissue and/or near or around visceral tissue ororgans, and non-neural tissue to treat acute pain, chronic pain, fecalor urinary incontinence, seizure disorders, movement disorders, obesity,spasticity, and to modulate other unpleasant neurological conditions.

In an example embodiment illustrated in FIG. 6, an electrode 30 may beimplanted on or adjacent to target tissue 12 comprising a majorperipheral nerve such as the tibial nerve 25 that extends down the leg26 of a patient 16. Depending on the application and the anatomy of thepatient, the electrode 30 may also be positioned on or just under theskin adjacent the target tissue 12. The electrode 30 may comprise asingle electrode or may comprise multiple electrodes 30. The electrodeor electrodes 30 may be positioned adjacent to the tibial nerve 25 at adesired location along its length. The electrode or electrodes 30 may bewrapped partially or completely around a section of the tibial nerve 25.The electrical signal generator 40 may be external to the patient 14 andelectrically coupled to the electrode 30 wirelessly, for exampleelectromagnetically via an antenna, inductively via an inductive coil,or via any other suitable wireless arrangement. Alternatively, theelectrical signal generator 40 can be electrically coupled to theelectrode 30 by a percutaneous or transcutaneous lead 18. Alsoalternatively, the electrical signal generator 40 can be implanted inthe patient 14 along with the electrode 30. With this arrangement, theexample embodiment of the neuromodulation system 10 can stimulate thetarget neural and non-neural tissue of the tibial nerve 25 to providetreatment for one or more diseases and syndromes including but notlimited to acute pain, failed back surgery syndrome, complex regionalpain syndrome, peripheral vascular disease and chronic limb ischemia,angina pain, diabetic pain, abdominal/visceral pain syndrome, brachialplexitis, phantom limb pain, intractable pain secondary to spinal cordinjury, mediastinal pain, Raynaud's syndrome, headache and migraine,cervical neuritis, post-herpetic neuralgia, vertigo, tinnitus, hearingloss and inflammatory pain such as arthritis, irritable bowel pain,osteoarthritis pain and fibromyalgia.

In an example embodiment of the neuromodulation system 10 the targettissue 12 may comprise neural and non-neural tissue of various internalorgans of the patient 14. In an example embodiment illustrated in FIGS.7-8, the target tissue 12 comprises neural and non-neural tissue of thestomach 27 of a patient 14. In this example embodiment, the electrodes30 of the neuromodulation system 10 can be implanted in or adjacent toneural and non-neural tissue of the stomach 27, for example on oradjacent to tissues of the wall of the stomach 27. With thisarrangement, the example embodiment of the neuromodulation system 10 canstimulate the neural tissue, e.g., parasympathetic nerves, andnon-neural tissue, muscle tissue, of the stomach 27. The exampleembodiment of the neuromodulation system 10 can thus provide treatmentfor obesity by inhibiting or mitigating the patient's 14 sensation ofhunger and/or modulating the patient's 14 gastric motor function, and/orprovide treatment to help control chronic nausea and vomiting by thepatient 14 associated with gastroparesis as a result of diabetes, amongother conditions.

In an example embodiment of the neuromodulation system 10 illustrated inFIG. 9, the target tissue 12 may comprise neural and non-neural tissueassociated with the bladder 28 of a patient 14, for example neural andnon-neural tissue of the sacral nerves 29 associated with the bladder28. The leads 18 and electrodes 30 of the neuromodulation system 10 maybe inserted into the patient 14 percutaneously and extended through oradjacent to the sacral foramen of the patient's 14 spine until theelectrodes 30 are positioned on or adjacent to the appropriate sacralnerve 29. With this arrangement, the example embodiment of theneuromodulation system 10 can stimulate the neural and non-neural tissueof the sacral nerves 29 associated with the muscles and organs, e.g.,the bladder 28, sphincter, and pelvic floor muscles that relate tobladder control and thus provide treatment to the patient 14 forconditions of overactive bladder, incontinence, and others.

In each of the example embodiments of the neuromodulation system 10described above, the electrical signal generator 40 generates electricalnoise stimulation signals which are delivered to the target tissue 12 ofthe patient 14 by the electrodes 30 in a way that optimizes andmaximizes the electric field in the target tissue 12. This is effectiveto provide long-lasting therapeutic results to the patient 14 byproducing long-term plastic functional change in the target tissue 12.The one or more sensors S1 and S2 may be implanted in or near the targettissue 12 of the patient 14 and may be located coincident with or nearthe electrodes 30. As described in further detail below, the sensors S1and S2 generate data that is indicative of a physical parameterassociated with the target tissue 12. In example embodiments, the datamay comprise data indicative of the temperature or impedance of thetarget tissue 12, or some other data indicative of the physical statusof the target tissue 12. Also as described in further detail below, thesensor data is received and used by the controller 50 to optimize andmaximize the electric field for treatment. The controller 50 also isconfigured to respond to the sensor data and to rapidly andautomatically take action by controlling the electrical signal generator40 to control and reduce the strength of the electric field as necessaryto help prevent potential tissue damage and patient discomfort withoutthe need for any direct input or feedback from the patient.

C. Implantable Electrode(s).

The electrodes 30 of the example embodiments of the neuromodulationsystem 10 may be implantable in the patient 14 in, on, or around thetarget tissue 12 to be treated. Depending on the application and theanatomy of the patient 14, the electrodes 30 may also be placed on orunder the skin of the patient 14. The electrodes 30 may be electricallycoupled to the electrical signal generator 40 by a suitable lead orleads 18. Alternatively, the electrodes 30 may be wirelesslyelectrically coupled to the electrical signal generator 40electromagnetically via a suitable antenna, inductively via a suitableinductive coil, or by any other suitable wireless arrangement.

The electrodes 30 receive the electrical noise stimulation signalsgenerated by the electrical signal generator 40 as described in furtherdetail below. The electrodes 30 produce an electric field forapplication to the target tissue 12, which as described can includeneural tissue, non-neural tissue, or a combination thereof.

The example embodiments may include a single electrode 30 or a pluralityof electrodes 30. The electrodes 30 can comprise one or moreelectrically conductive contacts integrated in a lead 18 andelectrically connected with one or more electrically conductive wires ofthe lead 18. The plurality of electrodes 30 can be arranged in variousconfigurations such as illustrated in FIGS. 18A-18D and 19A-19C forexample. In many cases, the electrodes 30 will be carried by and will belocated near the distal ends of percutaneous leads 18, such asillustrated in FIGS. 1-2 and 19A-19C. In other cases, the electrodes 30can be incorporated in a laminotomy or paddle lead 18, such asillustrated in FIGS. 18A-18D.

The shapes, sizes, and arrangements of the electrodes 30 and the spacingbetween electrodes 30 can be selected in order to generate one or moreelectric fields in and around the target tissue 12 having desiredproperties, depending at least in part on the nature and location of thetarget tissue, the condition being treated, and treatment beingprovided. The electrodes 30 can produce one or more electric fieldsalternately, consecutively, or simultaneously in and around the targettissue 12. In addition, and as described further below, a specificelectrode 30 and/or one or more pairs or other combinations ofelectrodes 30 can be selected to optimize and maximize the strength orintensity of the electric field in the target tissue 12 to provideoptimal therapeutic results and/or to control the strength of theelectric field in the target tissue 12 to prevent discomfort to thepatient 14 and damage to the target tissue 12. For example, specificelectrodes 30 or pairs or other combinations of electrodes 30 havingdifferent distances from and/or different orientations, e.g., angles,with respect to the target tissue 12 can be selected, which can affectthe impedance to current flow between the electrodes, the direction ofcurrent flow through the target tissue 12, the current density in thetarget tissue 12, and the strength and orientation of the electricfield(s) in the target tissue 12. Also for example, two or moreelectrodes 12 on the same or separate leads can be selected and tied orused together as a single electrode with greater surface area toincrease current density. See, e.g., FIG. 19A, electrodes 30 c, 30 g canbe selected together to comprise a common cathode with electrode 30 e asanode, FIG. 19B, electrodes 30 a, 30 c can be selected together tocomprise a common cathode with electrode 30 g as anode. Differentelectrodes 30 may also have different sizes and shapes, includingsurface areas, which can affect current density and flow and thestrength of the electric field in the target tissue 12.

Further, the one or more electrodes 30 can be configured to function asmonopolar, bipolar, or multipolar electrodes 30. For example, a pair ofelectrodes 30 can be configured to function in a bipolar fashion withone of the electrodes 30 acting as the anode and the other as thecathode, as illustrated in FIGS. 18A-18D and 19A-19 b for example. In aparticularly preferred bipolar arrangement, one of the electrodes 30 ofthe bipolar pair will be located in, on, or adjacent to the targettissue 12, and the other electrode 30 will be located in or onnon-excitable tissue, such as fat, fascia, or myelin tissue, in order toproduce an electric field in and around the target tissue 12.Alternatively, each electrode 30 of the bipolar pair can be located intissue, including non-excitable tissue, adjacent to the target tissue 12to produce an electric field in, through, and around the target tissue12. Preferably, regardless of the electrode 30 locations the electricfield produced will be optimized and maximized by applying to theelectrodes 30 an electrical noise stimulation signal having a relativelyhigh peak voltage, e.g., in a range of about 5V to about 200V, whilemaintaining an acceptable relatively low current flow, e.g., about 10 mAto about 300 mA or less, in the target tissue 12.

Alternatively, a plurality of electrodes 30 can function as anodes andanother electrode 30 as a cathode, or vice versa, in a multipolarfashion. The various electrodes 30 functioning in a bipolar ormultipolar manner can be carried on the same lead 18, as illustrated on18A-18D and FIG. 19C, or on separate leads 18 as illustrated in FIGS.19A and 19B, or a combination of both. Still further, one or moreelectrodes 30 can function as one or more monopolar cathodes located in,on, or around the target tissue 12 with another electrode 30 beingpositioned a substantial distance from the target tissue 12 such thatmost or all of the electric field is dissipated in tissues of thepatient 14. Alternatively, a case of the implantable enclosure 16 canfunction as the anode in a monopolar configuration.

D. Implantable Sensor(s).

The one or more implantable sensors S1, S2 of the example embodiments ofthe neuromodulation system 10 are implantable in the patient 14preferably in or near the target tissue 12. The sensors S1, S2 may belocated coincident with or near the electrodes 30. Each of the sensorsS1, S2 may comprise a separate physical unit. Alternatively, one or moreof the sensors S1, S2 may be integrated together and/or with one or moreof the leads 18 or electrodes 30.

The sensors S1, S2 are preferably electrically coupled and incommunication with the controller 50 via leads. The leads may comprisethe leads 18 or may be separate from the leads 18. Alternatively, one ormore sensors S1, S2 may be electrically coupled and in communicationwith the controller 50 wirelessly, for example using RF signaltransmission. The sensors S1, S2 may be coupled to and communicate withthe controller 50 via a sensor interface 56, which is illustrated inFIG. 11 and described in further detail below.

The sensors S1, S2 are adapted to generate sensor data that isindicative of one or more physical parameters preferably associated withthe target tissue 12. The sensor data may be generated and may becommunicated to the controller 50 synchronously or asynchronously, andcontinuously or at regular or irregular intervals of time. The sensorsS1, S2 may actively communicate the sensor data to the controller 50 orthe controller 50 may initiate communication with the sensors S1, S2 toretrieve the sensor data, e.g., by polling the sensors S1, S2.

In the example embodiments of the neuromodulation system 10, the sensorsS1, S2 preferably comprise one or more of a temperature sensor and animpedance sensor. The temperature sensor may comprise a thermistor, asolid state temperature sensor, or any other type of temperature sensorthat is suitable for use consistent with the objectives describedherein. The impedance sensor may comprise a miniature impedance orconductivity sensor. The impedance sensor may comprise a solid statetype sensor, such as an integrated circuit, or any other type ofimpedance or conductivity sensor that is suitable for use consistentwith the objectives described herein.

The reason why the sensors S1, S2 preferably comprise a temperaturesensor and/or an impedance sensor, and more preferably at least one ofeach type, is because the temperature and impedance of the target tissue12 of a patient 14 are physical parameters of the target tissue 12 thatexhibit specific values and ranges of values that provide a clearindication of the onset of potential damage and/or the occurrence ofdamage to the target tissue 12, and possible discomfort to the patient14. For example, persons skilled in the art will appreciate that thetypes of target tissue 12 of interest in connection with the exampleembodiments of the neuromodulation system 10 begin to experience damagedue to ablation at a temperature of about 42° C. Further, as the targettissue 12 begins to experience damage due to ablation, the impedancevalue of the tissue tends to rapidly decrease.

The temperature of the target tissue 12 varies in relation to the levelof current density and flow in the target tissue 12 induced byapplication of the electric field to the target tissue 12 by theelectrode 30. Thus, values and ranges of the temperature and impedanceparameters provided by the sensor data that indicate potential damage tothe target tissue 12 similarly indicate that the current density andflow induced by the electric field is too high. At the same time,relatively lower temperature and relatively higher impedance values andranges indicate that the current density and flow is not at a level topotentially cause damage to the target tissue 12.

Accordingly, the example embodiments of the neuromodulation system 10can use the temperature and impedance values of the target tissue 12provided by the sensor data to optimize and maximize the electric fieldintensity to provide optimal therapeutic results while not causingdamage to the target tissue 12 or discomfort to the patient 14. Theexample embodiments of the neuromodulation system 10 also can takeaction rapidly and automatically in response to temperature andimpedance values indicating potential damage to the target tissue 12 ordiscomfort to the patient 14 to control and if necessary reduce theelectric field intensity, including the current density and flow, toprevent such damage or discomfort even without any direct feedback fromthe patient 14. The sensors S1, S2 and the controller 50 describedfurther below thus comprise an automatic, closed-loop feedback system.

E. Electrical Signal Generator.

The electrical signal generator 40 of the example embodiments of theneuromodulation system 10 may be implantable in the patient 14, forexample within the implantable enclosure 16 as illustrated in FIGS. 1-5and 7-11. Alternatively, the electrical signal generator 40 may beexternal to the patient 14 as illustrated in FIG. 6.

The electrical signal generator 40 may comprise a separate physical unitor may integrated with the controller 50 and/or with one or more otherelectrical or electronic components described below in connection withthe electrical signal generator 40 and the controller 50. The electricalsignal generator 40 also may be integrated with an external controller60, which is described in further detail below.

The electrical signal generator 40 may be electrically coupled and incommunication with the electrodes 30 via one or more electrical leads 18as illustrated in FIGS. 1-5 and 7-10. Alternatively, the electricalsignal generator 40 may be wirelessly electrically coupled to theelectrodes 30 as illustrated in FIG. 6. The electrical signal generator40 may be wirelessly coupled to the electrodes 30 electromagneticallyvia a suitable antenna, inductively via a suitable inductive coil, or byany other suitable wireless arrangement. The electrical signal generator40 may be electrically coupled to the electrodes 30 via an electrodeinterface 54, which is illustrated in FIG. 11 and described in furtherdetail below.

The electrical signal generator 40 may also be electrically coupled andin communication with the controller 50. The electrical signal generator40 may be electrically coupled with the controller 50 via a wiredconnection or wirelessly.

The electrical signal generator 40 is adapted to generate electricalnoise stimulation signals for delivery to the target tissue 12 of thepatient 14 through the electrodes 30 in order to produce an electricfield in the target tissue 12 to stimulate or modulate the target tissue12 and thereby produce a therapeutic result as described herein. Morespecifically, the electrical signal generator 40 is adapted, undercontrol of and in response to the controller 50, to generate electricalnoise stimulation signals to optimize and maximize the electric field inthe target tissue 12 to produce an optimal therapeutic effect withoutresulting in data from the sensors S1, S2 indicating a value of thephysical parameter, e.g., temperature or impedance, associated withpotential damage to the target tissue 12 as described above.

The electrical signal generator 40 is preferably adapted andconfigurable to generate electrical noise stimulation signals havingcharacteristics determined by parameters and commands received by theelectrical signal generator 40 in real time, for example from thecontroller 50 or an operator, and/or determined by parameters andcommands contained in an embedded or external program or storage. Forexample, in response to and under the control of the controller 50 theelectrical signal generator 40 may be adapted and configured to startand stop the generation of the electrical noise stimulation signals sothat the example embodiments of the neuromodulation system 10 can applydoses of the electrical noise stimulation signals to the target tissue12 for selected durations of time and at selected intervals of time.

Also in response to and under the control of the controller 50, theelectrical signal generator 40 is preferably adapted and configurable toselectively generate electrical noise signals that have one or moreselected voltage peak values and that include all frequencies within aselected frequency spectrum or one or more selected bands of frequencieswithin the selected frequency spectrum with each selected band offrequencies having a selected bandwidth and center frequency. Theelectrical signal generator 40 also is preferably configurable toselectively generate electrical noise signals having one or moreselected peak voltage levels at one or more selected frequencies withina selected frequency spectrum and/or within one or more selectedfrequency bands within the spectrum. The particular characteristics ofthe electrical noise stimulation signals the electrical signal generator40 will be controlled to generate in practice depends on a variety offactors including the nature and location of the target tissue, thenature and severity of the condition being treated, and others. Forclarity, references to “peak voltage levels” of the electrical noisestimulation signals herein are to the monopolar peak values, i.e.,positive or negative peak values, of the electrical noise stimulationsignals and not to their peak-to-peak values which will be about twicethe peak values.

More specifically, the electrical signal generator 40 preferably isadapted to generate the electrical noise stimulation signals using oneor more forms of synthesis alone or in combination comprisingsubtractive synthesis, additive synthesis, component modeling synthesis,wavetable synthesis, linear arithmetic synthesis, phase distortionsynthesis, frequency modulation synthesis, and sample-based synthesis.Further, the electrical signal generator 40 preferably is adapted togenerate the electrical noise stimulation signals to include at leastone form of noise comprising Gaussian noise, white noise, pink noise,Brownian noise, red noise, and grey noise.

Also more specifically, the electrical signal generator 40 preferably isadapted and configurable to selectively generate the electrical noisestimulation signals with peak voltage values in the range of about 5V toabout 200V, and over a spectrum of frequencies in the range of about 50Hz., and more preferably about 100 Hz., to about 750 KHz. It will beappreciated that within these ranges the peak voltage values andfrequencies selected for use will depend on the nature and location ofthe tissue being stimulated or modulated and the nature and severity ofthe condition being treated, among other considerations.

Alternatively, other forms of noise stimulation signals can besubstituted for the electrical noise stimulation signals described aboveand other generators of such noise stimulation signals can besubstituted for the electrical signal generator to similarly stimulatethe target tissue 12, provide the same or similar treatments for thesame conditions, and achieve the same or comparable therapeutic effects.For example, magnetic, electromagnetic, or mechanically-induced noise,e.g., ultrasound noise, stimulation signals may be substituted for theelectrical noise stimulation signals and a magnetic, electromagnetic, orultrasound noise generator may be substituted for the electrical signalgenerator 40.

F. Controller.

The controller 50 of the example embodiments of the neuromodulationsystem 10 may be implantable in the patient 14, for example in theimplantable enclosure 16 as illustrated in FIGS. 1-5 and 7-11. Thecontroller 50 may comprise a separate physical unit or may integratedwith the electrical signal generator 40 and/or with one or more otherelectrical or electronic components described in connection with theelectrical signal generator 40 and the controller 50.

The controller 50 may comprise a general purpose microprocessor or adedicated purpose processor such as microcontroller. The microprocessorcan be a single-chip processor or implemented with multiple components.The controller also may comprise computer-readable storage for storingan operating system, program code or instructions, and data andparameters for controlling the operation of the controller 50. Thestorage may comprise random access memory (RAM), read only memory (ROM),and/or other volatile and/or non-volatile memory types. The programcode, data, etc. can also reside on a removable storage medium, forexample, CD-ROM, PC-CARD, USB drives, and may be loaded or installedwhen needed. Using instructions retrieved from storage, themicroprocessor can control the reception and manipulations of input datafrom components of the neuromodulaton system 10, such as the sensors S1,S2, and the output and communication of data, parameters, instructions,or commands to other components, such as the electrical signal generator40.

The controller 50 may be coupled with and may control an electrodeinterface 54, which may be enclosed within the implantable enclosure 16with the controller 50. The electrode interface 54 may comprise aseparate component or may be integrated with the controller 50. Theelectrode interface 54 is preferably interposed between the output ofthe electrical signal generator 40 and the electrodes 30. The electrodeinterface 54 is adapted to receive the electrical noise stimulationsignal from the electrical signal generator 40 as an input and toselectively connect the electrical noise stimulation signal to one ormore selected electrodes 30 via one or more leads 18 as outputs. Theelectrode interface 54 may comprise for example a MUX or a similarcontrollable selector for selectively connecting an input, e.g., theelectrical noise stimulation signal, to one or more selected outputs,e.g., the electrodes 30 via leads 18.

The controller 50 may be coupled with and may communicate with andreceive sensor data from the sensors S1, S2 through a sensor interface56, which may be enclosed within the implantable enclosure 16 with thecontroller 50. The sensor interface 56 may comprise a separate componentor may be integrated with the controller 50. The sensor interface 56 ispreferably adapted to receive the sensor data from the sensors S1, S2and to pre-process it as necessary for use by the controller 50. Forthat purpose, the sensor interface 56 may comprise one or more databuffers, filters, and any other components necessary or desirable forreceiving, cleaning, formatting, etc. the sensor data for use by thecontroller 50.

The controller 50 may be coupled with a communications interface 58,which may be enclosed within the implantable enclosure 16 with thecontroller 50. The communications interface 58 may comprise a separatecomponent or may be integrated with the controller 50. Thecommunications interface 58 is preferably adapted to allow thecontroller 50 to communicate with other components of the exampleembodiments of the neuromodulation system 10, such as for example theexternal controller 60 and user interface 62 illustrated in FIG. 10,and/or with other devices such as for example remote devices of thetelecommunications network 80 illustrated in FIG. 12 and describedbelow. The communications interface 58 preferably comprises thenecessary wired and/or wireless connections, interfaces, and protocolsto implement and support such communications. Suitable connections,interfaces, and protocols may include, for example, Ethernet, Wi-fi,USB, Bluetooth, as well as various other network, internet, and cellularconnections, interfaces, and protocols identified below in connectionwith the telecommunications network 80.

The controller 50 is preferably adapted and configurable toautomatically control the electrical signal generator 40 to generate anddeliver the electrical noise stimulation signals to the target tissue 12in a way that optimizes and maximizes the electric field in the targettissue 12 by maximizing the voltage component of the electric fieldwhile limiting the current density and flow in the target tissue 12 to asufficiently low level to not generate heating effects in the targettissue 12 that may cause damage to the target tissue 12 and discomfortto the patient 14. In this way, the controller 50 is able toautomatically control the electrical signal generator 40 to generate anddeliver electrical noise stimulation signals that optimize and maximizethe electric field in the target tissue 12 to produce an optimaltherapeutic effect but without the sensor data from the sensors S1, S2indicating a value of a physical parameter of the target tissue 12,e.g., temperature or impedance, associated with potential damage to thetarget tissue 12.

The present inventor has discovered that by optimizing and maximizingthe electrical field produced in neural, e.g., spinal cord or nervetissue, and non-neural, e.g., fascia or myelin, target tissue 12 in thisway (high voltage-low current density and flow), larger doses of theelectrical noise stimulation signals (i.e., higher voltage levels forlonger periods of time) can be delivered to the target tissue 12 withoutcausing overheating and damage to the target tissue 12. The presentinventor has further discovered that this in turn produces long-termplastic functional changes in the target tissue 12 that result in a morecomplete neural inhibition or blockade of neural function and that lastfor relatively long periods of time (days-to-weeks). As a result,relatively shorter and less frequent treatments can provide essentiallycontinuous effective therapeutic results without the need to applyelectrical modulation signals very frequently or substantiallycontinuously, and without the related need for substantially continuousdevice maintenance. The present inventor also has found that the targettissue 12 is less likely to develop a “tolerance” to the anatomicchanges produced with repeated dosing, which is a phenomenon thatplagues conventional spinal cord stimulation (SCS) systems.

In order to optimize and maximize the electric field to have thedescribed voltage and current characteristics described, the controller50 is preferably adapted and configurable to determine peak values ofimpedance to the flow of current in the target tissue 12 at one or morefrequencies within a selected portion or within the entire spectrum offrequencies of electrical noise stimulation signals the electricalsignal generator 40 is intended to potentially deliver to the targettissue 12 for treatment. Once the peak values of impedance and thecorresponding frequencies are determined, the controller 50 can controlthe electrical signal generator 40 to selectively generate and deliverto the target tissue 12 electrical noise stimulation signals in one ormore selected relatively narrower frequency bands having centerfrequencies corresponding to the peak values of impedance. Thecontroller 50 is also configurable to control the electrical signalgenerator 40 to adjust the characteristics of the noise signals within aselected band, such as for example the peak voltage values of thesignals, the center frequency of the band, and the width of the band. Inthis way, the example embodiments of the neuromodulation system 10 canoptimize and maximize the electric field produced in the target tissue12 by generating and delivering electrical noise stimulation signalswith peak voltage values selected to maximize the voltage component ofthe electric field while maintaining the current density and flow atrelatively low levels to prevent overheating and causing damage to thetarget tissue 12.

The controller 50 can be configured to determine the peak values ofimpedance and the corresponding frequencies at which they occur in anysuitable manner. A number of suitable example approaches are describedbelow. In each approach, the electrodes 30 are first inserted in thepatient 14 in conventional fashion and are positioned as desired inrelation to the target tissue 12 as described herein.

According to one approach, the controller 50 is preferably configurableto control the electrical signal generator 40 to generate and deliver tothe target tissue 12 via the electrode 30 an electrical noisestimulation signal that has a selected peak voltage level and a selectedfrequency spectrum comprising the entire range of frequencies ofelectrical noise stimulation signals that the electrical signalgenerator 40 is intended to potentially deliver to the target tissue 12for treatment.

For example, as illustrated in FIG. 13, the electrical noise stimulationsignal 70 can have a selected peak-peak voltage of about 300V withselected peak values of about +150V and −150V. It is noted that forclarity of illustration, FIG. 13 does not illustrate the entireelectrical noise stimulation signal 70 but only illustrates the portionsof the signal proximate to the peak values. As illustrated in FIG. 14,the power spectrum 72 of the electrical noise stimulation signal 70 issubstantially constant over the entire frequency bandwidth.

As described herein, the frequency spectrum of the electrical noisestimulation signal 70 can be selected based on various considerationsincluding but not limited to the nature of the tissue to be stimulatedor modulated, the nature and severity of the condition or disease beingtreated, the locations and orientations of the electrodes 30 in relationto the target tissue, and others. As previously described, preferredbandwidths may include about 50 Hz., and more preferably about 100 Hz.,to about 750 KHz.

The controller 50 is further configurable to control the electricalsignal generator 40 to generate and deliver to the target tissue 12 viathe electrodes 30 an electrical noise stimulation signal that comprisesa band of frequencies within the selected frequency spectrum with acenter frequency and a relatively narrow bandwidth. Both the centerfrequency and the bandwidth are selectable and can be adjusted orchanged by the controller 50. The bandwidth can be selected based on thedegree of resolution with which it is desired to determine the peakvalues of impedance and the corresponding frequencies at which theyoccur. For example, the bandwidth might be selected to be in the rangeof about 100 Hz. to about 1 KHz. Alternatively, the controller 50 can beconfigurable to generate and deliver a non-noise electrical stimulationsignal comprising a single selectable frequency, i.e., a periodicsignal.

The controller 50 is further configurable to control the electricalsignal generator 40 to successively generate and deliver the electricalnoise stimulation signals with the same relatively narrow bandwidth butwith a plurality of different center frequencies that span a selectedportion or the entire spectrum of frequencies the electrical signalgenerator is intended to potentially deliver to the target tissue 12 fortreatment. The controller 50 can be configured to control the electricalsignal generator 40 to continuously sweep or scan the center frequencyacross the entire frequency spectrum or a selected portion or portionsof the entire spectrum, and alternatively may control the electricalsignal generator 40 to adjust the center frequency in one or more fixedincrements or steps. For example, the controller 50 can be configured tocontrol the electrical signal generator 40 to continuously or discretelyscan or sweep the center frequency from the lowest frequency to thehighest frequency of the entire spectrum or a selected portion orportions of the entire spectrum. Alternatively, the controller 50 can beconfigurable to control the electrical signal generator to continuouslyor discretely scan a non-noise electrical stimulation signal comprisinga single selectable frequency, i.e., a periodic signal, across theentire spectrum or a selected portion or portions thereof.

The controller 50 is configurable to receive and monitor sensor datafrom the sensors S1, S2 while the electrical noise stimulation signalsare being delivered to the target tissue 12 via the electrodes 30. Thecontroller 50 is configurable to determine from the sensor data theimpedance to current flow in the target tissue 12 at each centerfrequency or at a subset of the center frequencies of the narrow band ofelectrical noise stimulation signals. Accordingly, the values ofimpedance may be substantially continuous or may be a series of discretevalues. FIGS. 15A-15C illustrate several examples of the impedance (Z)74 with respect to frequency and demonstrate how the magnitude of theimpedance (Z) 74 can vary as the center frequency of the narrow band ofelectrical noise stimulation signals is scanned or swept substantiallycontinuously across the selected frequency spectrum. The two-headedarrow in each figure indicates that the figure is illustrating only aportion of the values of impedance (Z) 74 for a corresponding portion ofthe scanned or swept frequencies in either direction.

The controller 50 is configurable to determine from the impedance (Z)sensor data a peak or peaks of greatest magnitude and the frequencies atwhich they occurred. The controller 50 is also preferably configurableto determine the center frequency (f_(c)) and lower and upperfrequencies (f₁, f₂) for each of the peak or peaks. The center frequency(f_(c)) generally will correspond to the center frequency of the narrowfrequency band of electrical noise stimulation signals that produced thepeak, but may also be different for various reasons. Similarly, thelower and upper frequencies (f₁, f₂) of the peaks will generallycorrespond to the lower and upper frequencies of the narrow frequencybands of electrical noise stimulation signals that produce the peaks,but may also be different. The band of frequencies corresponding to apeak, like the band of frequencies of the electrical noise stimulationsignals that produced the peak comprise a relatively smaller subset ofthe entire frequencies of the selected frequency spectrum. The upper andlower frequencies (f₁, f₂) of each peak can be determined in any numberof manners, including for example treating the shape of the peak as abandpass filtered signal and applying conventional calculations fordetermining filter roll-off or cut-off frequencies.

Various impedance peaks with various values of magnitude may occur atvarious different frequencies within the entire spectrum or range offrequencies scanned or swept. For example, FIG. 15A illustrates a firstpeak of impedance (Z) 74 having a first value of magnitude and a centerfrequency (f_(c)) at a corresponding first frequency value, FIG. 15Billustrates a second peak of impedance (Z) 74 having a second value ofmagnitude and a different center frequency (f_(c)) at a correspondingsecond frequency value, and FIG. 15C illustrates a third peak ofimpedance (Z) 74 having a third value of magnitude and a centerfrequency (f_(c)) at a corresponding third frequency value. Thecontroller 50 preferably is configurable to discriminate between orfilter the detected impedance peaks and to retain for use in providingtreatment only those center frequencies and relatively narrow frequencybands corresponding to peaks with sufficient magnitudes of impedance toeffectively optimize and maximize the electric field with the desiredcharacteristics of voltage and current as described herein. For example,impedances in the range of about 200 ohms to about 10,000 ohms may besuitable for use depending on various factors including the selectedvalue of peak voltage of the electrical noise stimulation signals to beapplied, the target tissue, the nature and severity of the condition tobe treated, the configuration and locations of the electrodes relativeto the target tissue, and others. For clarity, it will be appreciatedthat the foregoing range of impedance values (Z) is contemplated toinclude impedance contributions of the target tissue, tissue interface,leads, and electrodes.

According to another approach to determine the peak values of impedanceand the corresponding frequencies and frequency bands at which theyoccur, the controller 50 is preferably configurable to control theelectrical signal generator 40 to generate and deliver to the targettissue 12 via the electrode 30 an electrical noise stimulation signalsuch as illustrated in FIGS. 13-14 that has a selected peak voltagelevel and a selected frequency spectrum comprising the entire range offrequencies that the electrical signal generator 40 is intended topotentially deliver to the target tissue 12 for treatment. Theelectrical noise stimulation signals can have the same parameters as theapproach described above.

The controller 50 is configurable to receive and monitor sensor datafrom the sensors S1, S2 while the electrical noise stimulation signalsare being applied to the target tissue 12 via the electrodes 30. Thecontroller 50 is preferably configurable to determine from the sensordata the impedance to current flow in the target tissue 12 at one or aplurality of frequencies and frequency bands within the selectedfrequency spectrum. For example, the controller 50 can be configured toapply a bandpass filter to the impedance sensor data to determine themagnitude of the impedance to the electrical noise stimulation signalscomprising one or a plurality of narrow frequency bands. The bandpassfilter can have a selected pass band and a discretely or continuouslyvariable center frequency. The bandpass filter may be applied to theimpedance sensor data in real time or the sensor data may be stored forprocessing with the filter. The filter can produce a substantiallycontinuous set of impedance values in relation to frequency similar tothat shown in FIGS. 15A-15C or a set of discrete values at discretevalues of frequency. The controller 50 can be configured to process thefiltered impedance sensor data in a manner similar to that describedabove to determine the peaks in impedance, the magnitudes of theimpedance at the peaks, and the corresponding frequencies and frequencybands at which they occurred for use in optimizing and maximizing theelectric field to provide treatment.

It is noted that both approaches described above are examples and thatthe peaks and peak magnitudes of impedance and the frequencies andfrequency bands at which they occur can be determined in other ways thatdo not depart from the broad concepts present in the example embodimentsof the neuromodulation system 10 described herein. It is further notedthat regardless of the approach used, it is preferred that thecontroller 50 monitor the sensor data from the sensors S1, S2 while theapproach is being carried out. That way if the sensor data correspondingto a physical parameter, e.g., impedance or temperature, of the targettissue 12 assumes a value indicative of potential damage to the targettissue 12, for example excessive heating, the controller 50 can rapidlyand automatically respond and take action by controlling the electricalsignal generator 40 to control the strength of the electric field, whichmay include reducing current density and flow, to prevent damage to thetarget tissue 12 and discomfort to the patient 14. The sensors S1, S2and the controller 50 thus comprise an automatic, closed-loop feedbackcontrol system that does not require any direct feedback from thepatient 14. In addition, in order to further reduce the risk of causingdamage to the target tissue 12 or patient 14 discomfort whiledetermining the impedance peaks and peak magnitudes, the controller 50can control the electrical signal generator 40 to generate and deliverthe electrical noise stimulation signals with a peak voltage value thatis less than the peak voltage value that may be used to optimize andmaximize the electric field for actual treatment.

A number of example approaches to control the strength of the electricfield are described in further detail below. The same approaches areequally applicable when the electrical noise stimulation signal is beingapplied to the target tissue 12 in advance of treatment to determine theimpedance peaks and when the electrical noise stimulation signal isbeing applied to the target tissue 12 to provide treatment. Further, thesame approaches are applicable to control the electric field to optimizeand maximize its strength by maximizing the voltage component whilelimiting current density and flow to provide optimal treatment to thetarget tissue 12, and to reduce its strength, including reducing currentdensity and flow, to prevent damage to the target tissue 12 anddiscomfort to the patient 14.

With reference to FIGS. 18A-18D and 19A-19C, it is also noted that inconnection with determining the peaks and peak values of impedance andthe frequencies at which they occur, the controller 50 is preferablyconfigurable to control the electrode interface 54 as described above toselect a plurality of different combinations of electrodes 30 to deliverthe electrical noise stimulation signals or a non-noise electricalstimulation signal to the target tissue 12. As previously described, thelocations, orientations, and distances of the electrodes 30 in relationto the target tissue 12 can have a substantial effect on the impedanceto current flow and the strength of the electric field in the targettissue 12 in response to a particular electrical noise stimulationsignal.

The controller 50 can be configured to carry out either approachdescribed above a plurality of times using a plurality of differentcombinations of electrodes 30 to determine the peaks and peak values ofimpedance and the corresponding frequencies for each of a plurality ofcombinations of electrodes 30. For example, with respect to thepaddle-type leads 18 and electrodes 30 illustrated in FIG. 18A-18D, thecontroller 50 can be configured to determine the peaks and peak valuesand corresponding frequencies using one, some or all of selectedelectrode combinations 30 a-30 d, 30A-30 e, 30 a-30 f, 30 c-30 d, 30c-30 e, 30 c-30 f, 30 b-30 d, 30 b-30 e, 30 b-30 f, 30 a-30 b, 30 a-30 cor other selected combinations in monopolar, bipolar, or multipolarconfigurations. Similarly, with respect to the percutaneous leads 18 andelectrodes 30 as illustrated in FIGS. 19A-19C, the controller 50 can beconfigured to determine the peaks, peak values, and correspondingfrequencies using one, some or all of selected electrode combinations 30a-30 d, 30 a-30 f, 30 b-30 e, 30 g-30 e, 30 c-30 f, 30 a-30 g, 30 c-30g, 30 c/30 g-30 e, 30 a-30 c, 30 a-30 g, 30 a/30 c-30 g, 30 b-30 g orother selected combinations in monopolar, bipolar, or multipolarconfigurations.

Further, the selected combinations of electrodes 30 may be present ondifferent leads 18 as illustrated in FIGS. 19A-19B, and on the sameleads 18 as illustrated in FIGS. 18A-18D and 19C. The selectedcombinations of electrodes 30 may comprise combinations with one or moreelectrodes 30 located in, on, or adjacent to the target tissue 12 andone or more electrodes 30 located at a distance from the target tissue12 as illustrated in FIGS. 18A-18C and 19A-19B, e.g., in non-neuraltissue such as myelin or fascia. The selected combinations of electrodes30 may comprise combinations with all of the electrodes 30 located in,on, or adjacent to the target tissue 12 as illustrated in FIGS. 18D and19C.

When the example embodiments of the neuromodulation system 10 aresubsequently used to provide treatment, the controller 50 can beconfigured to use the information regarding the peaks and peak values ofimpedance and the corresponding frequencies at which they occurred foreach of the plurality of selected combinations of electrodes 30 toselect a specific combination of electrodes 30 to deliver the electricalnoise stimulation signals to the target tissue 12 that will optimize andmaximize the electric field in the target tissue 12 with the desiredvoltage and current characteristics described herein to produce optimaltherapeutic results. This can be done either under operator control orautomatically by the controller 50.

To provide treatment to a patient 14, the controller 50 can beconfigured to control the electrical signal generator 40 to optimize andmaximize the electric field in the target tissue 12 with the desiredvoltage and current characteristics to provide optimal therapeuticresults without the sensor data indicating potential damage to thetarget tissue 12 in a number of ways. In one example approach, thecontroller 50 can be configured to control the electrical signalgenerator 40 to limit the dose of the electrical noise stimulationsignals and thus the electric field to the target tissue 12 by limitingthe duration of time the electrical signal generator 40 delivers theelectrical noise stimulation signals with peak voltage values in thepreferred range described herein to the target tissue 12. This in turnlimits the current density and flow over time and limits heating of thetarget tissue 12, thus producing optimal therapeutic effects without thesensor data indicating a value of the physical parameter, e.g.,temperature or impedance, associated with potential damage to the targettissue 12 or discomfort to the patient 14. For example, the presentinventor has found that in some instances electrical stimulation signalswith peak voltage values in the preferred range can be delivered to thetarget tissue 12 to produce an optimized and maximized electric field indoses as short as four (4) minutes and provide effective relief frompain for up to a week or more without causing any damage to the targettissue 12 or discomfort to the patient 14.

In another example approach, the controller 50 can be configured tooptimize and maximize the electric field in the target tissue 12 bycontrolling the electrical signal generator 40 to generate and deliverthe electrical noise stimulation signals to the target tissue 12 in oneof the narrow frequency bands of the plurality of narrow frequency bandspreviously determined to correspond to peak values of impedance of thetarget tissue 12. Further, the controller 50 can be configured tocontrol the electrical signal generator 40 to adjust the centerfrequency of the frequency band upwardly or downwardly to furthercontrol and adjust the electric field and to monitor the sensor data todetermine the effects of the adjustments on the impedance, voltage,current density and flow, and temperature of the target tissue 12 tooptimize and maximize the electric field in the target tissue 12.

In another example approach, the controller 50 can be configured tooptimize and maximize the electric field in the target tissue 12 byselecting a first frequency band corresponding to a first peak value ofimpedance of the target tissue 12 from the plurality of frequency bandspreviously determined to correspond to peak values of impedance of thetarget tissue 12. The controller 50 can be further configured to controlthe electrical signal generator 40 to generate and deliver theelectrical noise stimulation signals to the target tissue 12 in theselected first frequency band. The controller 50 can further beconfigured to monitor the sensor data, make a determination regardingthe characteristics of the electric field produced in the target tissue12 by the electrical noise stimulation signals in the first frequencyband, select a second frequency band corresponding to a second peakvalue of impedance of the target tissue 12, and control the electricalsignal generator 40 to generate and deliver the electrical noisestimulation signals to the target tissue 12 in the selected secondfrequency band. The controller 50 can be configured to continue toselect additional frequency bands corresponding to previously determinedpeak values of impedance and control the electrical signal generator 40to generate and deliver electrical noise stimulation signals in each ofthe selected bands until the most optimized electric field, e.g. highestvoltage component with acceptably low current density and flow, isproduced in the target tissue 12.

In another example approach, the controller 50 can be configured tocontrol the electrode interface 54 to select a first electrode 30 orcombination of electrodes 30 from the plurality of electrodes 30 andplurality of possible combinations of electrodes 30 as described above.The controller 50 can be further configured to control the electricalsignal generator 40 to generate the electrical noise stimulation signaland deliver it to the target tissue 12 via the first selected electrode30 or combination of electrodes 30 to produce the electric field in thetarget tissue 12. The controller 50 can further be configured to monitorthe sensor data, make a determination regarding the characteristics ofthe electric field produced in the target tissue 12 using the firstselected electrode 30 or combination of electrodes 30, select a secondelectrode 30 or combination of electrodes 30, and control the electricalsignal generator 40 to generate and deliver the electrical noisestimulation signals to the target tissue 12 using the second electrode30 or combination of electrodes 30. The controller 50 can be configuredto continue to select additional electrodes 30 or combinations ofelectrodes 30 to deliver the electrical noise stimulation signals to thetarget tissue until the most optimized electric field, e.g. highestvoltage component with acceptably low current density and flow, isproduced in the target tissue 12.

It will be appreciated that any one or more of the above-describedapproaches, as well as others, can be employed alone or in combination.It will also be appreciated that the controller 50 can also beconfigured to control the electrical signal generator 40 to change oradjust the peak voltage values of the electrical noise stimulationsignals in combination with any one or more of the above-described orother approaches.

It also will be appreciated from the foregoing descriptions of exampleapproaches to optimize and maximize the electric field that thecontroller 50 is adapted and configured to optimize and maximize theelectric field automatically in response to the sensor data even withoutany direct feedback from the patient 14. In addition and if desired, anoperator or user of the example embodiments of the neuromodulationsystem 10 can further adjust the optimized electric field based onsubjective input regarding patient 14 sensations in response toapplication of the automatically optimized electric field to the targettissue 12 in order to optimize the sensations as subjectively felt bythe patient 14 and the patient's subjective treatment experience. Forexample, an operator or user can have a patient 14 being treated compareand describe the sensations the patient is subjectively feeling as thecenter frequency of a selected frequency band is adjusted, as differentfrequency bands are selected, and/or as different combinations ofelectrodes 30 are selected. The operator or user can then providecorresponding inputs to the controller 50 to control the electricalsignal generator 40 to adjust the parameters of the electrical noisestimulation signals and/or to adjust the selection of electrodes 30 inorder to adjust the electric field produced in the target tissue 12 andoptimize the patient's subjectively felt sensations and treatmentexperience.

Further with regard to optimizing and maximizing the electric field, thecontroller 50 is preferably configured to control the electrical signalgenerator 40 to generate the electrical noise stimulation signals withpeak voltage values in the range of about 5V to about 200V over afrequency spectrum of about 50 Hz., and more preferably about 100 Hz.,to about 750 KHz. Within each range, the values of peak voltage and thefrequencies selected for treatment will depend on the nature andlocation of the tissue being stimulated or modulated and the nature andseverity of the condition being treated, among other considerations.

Still further, within the foregoing voltage and frequency ranges, thecontroller 50 also is preferably configured to control the electricalsignal generator 40 to generate and deliver the electrical noisestimulation signals to produce optimized and maximized electric fieldsin the target tissue 12 having intensity values in the range of about1,000V/m to about 500,000V/m with current flow in the range of about 10mA to about 300 mA or less.

As described above, the controller 50 is preferably configured tomonitor the sensor data produced by the sensors S1, S2 both while theelectrical noise stimulation signals are being provided to the targettissue 12 to determine the peaks and peak values of impedance and tostimulate or modulate the target tissue 12 to provide treatment. Thecontroller 50 is preferably configured to rapidly and automaticallyrespond to the sensor data indicating a value of the physical parameter,e.g., impedance and/or temperature, associated with potential damage tothe target tissue 12 and to rapidly and automatically take an action tocontrol and reduce the strength of the electric field, and/or reduce thecurrent density and flow, to prevent damage to the target tissue 12 anddiscomfort to the patient 14. Thus, as noted previously, the sensors S1,S2 and the controller 50 comprise an automatic, closed-loop feedbacksystem that does not require direct feedback from the patient 14.

For example, as illustrated in FIG. 16-17 while the electrical noisestimulation signals are being applied to the target tissue 12 in aselected frequency band, the value of the monitored impedance (Z) 76derived from the sensor data produced by one or more of the sensors S1,S2 may be expected to remain relatively stable. Similarly, the value ofthe monitored temperature 78 of the target tissue 12 derived from thesensor data produced by one or more of the sensors S1, S2 may beexpected to remain relatively stable and perhaps to rise somewhat withlarger doses, e.g., longer durations or higher peak voltage values, ofthe electrical noise stimulation signals. However, if or when the valueof the monitored temperature 78 rises to a predetermined level or valueindicative of potential damage to the target tissue 12 as illustrated bythe horizontal dashed line in FIG. 17, a temperature action point 79 isreached. Similarly, if or when the value of the monitored impedance 76decreases to a predetermined level or value indicative of potentialdamage to the target tissue 12 as illustrated by the horizontal dashedline in FIG. 16, an impedance action point 77 is reached. The controller50 is configurable to determine when an action point has been reachedand to rapidly and automatically take action as described herein.

The predetermined level or value of temperature that corresponds to atemperature action point 79 can be a predetermined relative or absolutevalue, such as 42° C., or a range of temperatures, or another derivedparameter of temperature such as an average, mean, or slope. Similarly,the predetermined level or value of impedance that corresponds to animpedance action point 77 can be a predetermined absolute or relativevalue, such as a 50% decrease, or a range of absolute or relativeimpedance values, or another derived parameter of impedance such as anaverage, mean, or slope.

Typically, it can be expected that a relatively rapid rise in the valueof temperature and a relatively rapid decrease in the value of impedancewill correspond in time and together indicate potential damage to thetarget tissue 12, but not always. Accordingly, the controller 50 may beconfigured to monitor and use the sensor data values for either physicalparameter, but preferably both, in determining whether and when to takeaction.

Regarding the actions the controller 50 may take to control the strengthof the electric field or the current density and flow to prevent damageto the target tissue 12 and discomfort to the patient 14, it will beappreciated that any one or more or a combination of the above-describedactions for controlling the electric field to optimize and maximize itcan also be used to control the electric field to reduce its strength,including reducing the current density and current flow in the targettissue 12. Thus, any one or more or a combination of such approaches,e.g., adjusting center frequency, selecting different frequency bands,and selecting different electrodes, can comprise the action or actionstaken by the controller 50 in response to the sensor data indicating avalue of the physical parameter, e.g., temperature and impedance,associated with potential damage to the target tissue 12.

G. User Interface.

As illustrated in FIG. 10, the example embodiments of theneuromodulation system 10 may but need not necessarily include a userinterface 62 external to the patient 14. If included, the user interface62 may comprise a conventional computer or computer system, and/or oneor more peripherals, such as a conventional display, keyboard, keypad,and pointing device, such as a mouse. The user interface 62 also maycomprise a mobile device 84, such as a tablet computer, as illustratedin FIG. 12. The user interface may be adapted and configured to enable auser or operator to interact with the controller 50 either directly orindirectly via an external controller 60, which is described furtherbelow.

The user interface 62 may comprise a separate unit or component and maybe integrated in whole or in part with the external controller 60. Theuser interface 62 can be used to communicate with the controller 50 andwith the external controller 60 to enable powering the exampleembodiments of the neuromodulation system 10 up and down, to performsystem setup, to enter start/stop commands for generation of theelectrical noise stimulation signals, to make adjustments to theparameters and characteristics of the electrical noise stimulationsignals either for future use or in real time, and to otherwise enableuser or operator control of the example embodiments of theneuromodulation system 10. The user interface 62 also can be adapted andconfigured to receive and display various items of information to enablea user or operator to monitor the status, operation and functionality ofthe example embodiments of the neuromodulation system 10 and ifnecessary intervene. Such information can include, for example, sensordata, such as temperature and impedance values, identification of theselected electrodes, and various characteristics of the electrical noisestimulation signal, such as voltage level, current intensity level,field intensity, center frequency, and frequency bandwidth. Suchinformation also can include treatment information including the dosetime selected and the time remaining. The information also can includeinformation concerning system status such as the remaining charge levelof batteries comprising an internal power source 52, which is describedfurther below, internal temperature of the implantable enclosure 16,etc.

H. External Controller.

As illustrated in FIG. 10, the example embodiments of the neuromodulatorsystem 10 may but need not necessarily include an external controller 60that is external to the patient 14. If included, the external controller60 may comprise a conventional computer or computer system, and may alsocomprise a mobile device 84, such as a tablet computer, as illustratedin FIG. 12. The external controller 60 may comprise a separate unit orcomponent and may be integrated in whole or in part with the userinterface 62.

The external controller 62 may be electrically coupled with and may beadapted and configured to communicate with the controller 50 via wireleads 65 or wirelessly. Wireless communication may be by any suitablewireless arrangement including electromagnetically via RF transmissionwith suitable antennas, inductively via a suitable inductive coilarrangement, or by any other suitable wireless arrangement. Similarly,the external controller 60 also may be coupled to and adapted andconfigured to communicate with remote devices via telecommunicationsnetwork 80 as illustrated in FIG. 12.

The external controller 60 can be adapted and configured to incorporatesome or all of the functions and operability of the controller 50described herein such that in some embodiments, an implantablecontroller 50 may not be present. Alternatively, the external controller60 in combination with the user interface 62 may be adapted andconfigured to enable a user or operator to externally control some orall of the functions and operations of the controller 50, including forexample the generation and control of the electrical noise stimulationsignals, selection of electrodes 30 and application of the electricalnoise stimulation signals to target tissue 12, and monitoring of sensordata generated by sensors S1, S2.

The external controller 60 also can be adapted and configured to controlin whole or in part the use of an external power source 64, which isillustrated in FIG. 10 and described further below, to provide powerremotely to the components within the implantable enclosure 16illustrated in FIG. 11. The external controller 60 can be adapted andconfigured to control use of the external power source 64 to provide asource of power for the internal power source 52, for example if theinternal power source comprises a transformer or voltage converter, andto provide power to recharge internal power source 52 if the internalpower source 52 comprises rechargeable batteries. In embodiments withoutthe internal power source 52, the external controller 60 can be adaptedand configured to control use of the external power source 64 todirectly provide power to the other components of the implantableenclosure 16, including the electrical signal generator 40 to generatethe electrical noise stimulation signals. Further, in embodiments inwhich the electrical signal generator 40 is external to the patient 14,the external controller 60 can be adapted and configured to control useof the external power source 64 to directly provide power to theexternal electrical signal generator 40.

I. Power Sources.

An internal power source 52 may be enclosed within the implantableenclosure 16 and be implantable in a patient 14. The internal powersource 52 may be electrically coupled to and provide operating power tothe electrical signal generator 40, controller 50, and other componentsenclosed within the implantable enclosure 16, including the electrodeinterface 54, sensor interface 56, and communications interface 58 tothe extent needed.

The internal power source 52 may comprise an internal source of power,such as a transformer, voltage converter, or the like that is fed by anexternal source of power, such as external power source 64 illustratedin FIG. 11 and described below. In that case, the internal power source52 may be coupled to and receive power from the external source of powervia a wired connection or wirelessly, for example via a suitableinductive coil arrangement.

Preferably, however, the internal power source 52 will comprise aself-contained source of power such as a suitable battery or batteries.Further, the battery or batteries preferably will be of the rechargeabletype. Suitable batteries may include batteries of the lithium ion,lithium air, lithium/iodine, and lithium/manganese oxide types which arecommercially available from numerous sources. The battery or batterieswill preferably be rechargeable either via a wired connection to anexternal source of power, such as the external power source 64, orwirelessly, for example via a suitable inductive coil arrangement.

The external power source 64 is located external to the patient 14 andpreferably is adapted to provide operating power for the externalcontroller 60 and the user interface 62. The external power source 64also is preferably adapted to function as a source of external power tothe internal power source 52 as described above. In embodiments in whichthere is no internal power source 52, the external power source 64 alsopreferably will be adapted to provide power directly to the othercomponents of the implantable enclosure 16, including the electricalsignal generator 40 to generate the electrical noise stimulationsignals. Further, in embodiments in which the electrical signalgenerator 40 is external to the patient 14, the external controller 60will preferably be adapted to provide power directly to the externalelectrical signal generator 40. The external power source 64 maycomprise any suitable source of power including but not limited to oneor more connections to an external power grid, a generator, or one ormore batteries.

J. Exemplary Telecommunications Networks.

With reference to FIG. 12, the example embodiments of theneuromodulation system 10 may be utilized upon or in connection with anytelecommunications network 80 capable of transmitting data includingvoice data and other types of electronic data. For example, thecontroller 50 and the external controller 60 of the example embodimentsof the neuromodulation system 10 may connect and communicate with remotedevices using the telecommunications network 80. Examples of suitabletelecommunications networks 80 for the example embodiments of theneuromodulation system 10 include but are not limited to global computernetworks (e.g. Internet), wireless networks, cellular networks,satellite communications networks, cable communication networks (via acable modem), microwave communications networks, peer-to-peer networks,local area networks (LAN), wide area networks (WAN), campus areanetworks (CAN), metropolitan-area networks (MAN), and home area networks(HAN). The communications interface 58 and the external controller 60 ofthe example embodiments of the neuromodulation system 10 may comprisethe appropriate modems or other interfaces and may implement theappropriate protocols to enable the example embodiments of theneuromodulation system 10 to communicate with remote devices over thetelecommunications network 80. The example embodiments of theneuromodulation system 10 may communicate via a singletelecommunications network 80 or multiple telecommunications networks 80concurrently. Various protocols may be utilized by the electronicdevices for communications such as but not limited to HTTP, SMTP, FTPand WAP (Wireless Application Protocol). The example embodiments of theneuromodulation system 10 may be utilized in connection with variouswireless networks such as but not limited to 3G, 4G, LTE, CDPD, CDMA,GSM, PDC, PHS, TDMA, FLEX, REFLEX, IDEN, TETRA, DECT, DATATAC, andMOBITEX. The example embodiments of the neuromodulation system 10 mayalso be utilized with online services and internet service providers.

The Internet is an exemplary telecommunications network for the exampleembodiments of the neuromodulation system 10 to operate upon or inconnection with. The Internet is comprised of a global computer networkhaving a plurality of computer systems around the world that are incommunication with one another. Via the Internet, the computer systemsare able to transmit various types of data between one another. Thecommunications between the computer systems may be accomplished viavarious methods such as but not limited to wireless, Ethernet, cable,direct connection, telephone lines, and satellite.

K. Central Communication Unit.

The example embodiments of the neuromodulation system 10 may be incommunication with a central communication unit 82. The centralcommunication unit 82 may be comprised of any central communication sitewith which communications are preferably established. The centralcommunication unit 82 may be comprised of a server computer, cloud basedcomputer, virtual computer, personal computer or other computer systemcapable of receiving and transmitting data via IP networks and/or thetelecommunication network. As can be appreciated, a modem or othercommunication device may be required between each of the centralcommunication unit 82 and the corresponding telecommunications network80. The central communication unit 82 may be comprised of any electronicsystem capable of receiving and transmitting information (e.g. voicedata, computer data, etc.).

L. Mobile Device.

The example embodiments of the neuromodulation system 10 may becomprised of in part or may be in communication with a mobile device 84.For example, all or part of the external controller 60 illustrated inFIG. 10 and described above may be comprised of the mobile device 84.The mobile device 84 may be comprised of any type of computer forpracticing the various aspects of the example embodiments of theneuromodulation system 10. For example, the mobile device 84 can be apersonal computer (e.g. APPLE® based computer, an IBM based computer, orcompatible thereof) or tablet computer (e.g. IPAD®). The mobile device84 may also be comprised of various other electronic devices capable ofsending and receiving electronic data including but not limited tosmartphones, mobile phones, telephones, personal digital assistants(PDAs), mobile electronic devices, handheld wireless devices, two-wayradios, smart phones, communicators, video viewing units, televisionunits, television receivers, cable television receivers, pagers,communication devices, and digital satellite receiver units.

The mobile device 84 may be comprised of any conventional computer. Aconventional computer preferably includes a display screen (or monitor),a printer, a hard disk drive, a network interface, and a keyboard. Aconventional computer also includes a microprocessor, a memory bus,random access memory (RAM), read only memory (ROM), a peripheral bus,and a keyboard controller. The microprocessor is a general-purposedigital processor that controls the operation of the computer. Themicroprocessor can be a single-chip processor or implemented withmultiple components. Using instructions retrieved from memory, themicroprocessor controls the reception and manipulations of input dataand the output and display of data on output devices. The memory bus isutilized by the microprocessor to access the RAM and the ROM. RAM isused by microprocessor as a general storage area and as scratch-padmemory, and can also be used to store input data and processed data. ROMcan be used to store instructions or program code followed bymicroprocessor as well as other data. A peripheral bus is used to accessthe input, output and storage devices used by the computer. Thesedevices may include a display screen, a printer device, a hard diskdrive, and/or a network interface. The display screen comprises anoutput device that displays images of data provided by themicroprocessor via the peripheral bus or provided by other components inthe computer. A keyboard controller is used to receive input from thekeyboard and send decoded symbols for each pressed key to microprocessorover bus. The keyboard is used by a user to input commands and otherinstructions to the computer system. Other types of user input devicescan also be used in conjunction with the example embodiments of theneuromodulation system 10. For example, pointing devices such as acomputer mouse, a track ball, a stylus, or a tablet to manipulate apointer on a screen of the computer system. All or part of the userinterface 62 of the example embodiments of the neuromodulation system 10illustrated in FIG. 10 and described above can be comprised in whole orin part by the display screen, keyboard, and/or other input devicesdescribed above. The printer device when operating as a printer providesan image on a sheet of paper or a similar surface. The hard disk drivecan be utilized to store various types of data. The microprocessortogether with an operating system operate to execute computer code andproduce and use data. The computer code and data may reside on RAM, ROM,or hard disk drive. The computer code and data can also reside on aremovable program medium and loaded or installed onto computer systemwhen needed. Removable program mediums include, for example, CD-ROM,PC-CARD, USB drives, floppy disk and magnetic tape. The networkinterface circuit is utilized to send and receive data over a networkconnected to other computer systems. An interface card or similar deviceand appropriate software implemented by microprocessor can be utilizedto connect the computer system to an existing network and transfer dataaccording to standard protocols.

M. Operation of Preferred Embodiment.

In an example of use of an example embodiment of the neuromodulationsystem 10, one or more leads 18 with electrodes 30 may be inserted in apatient in conventional fashion and positioned in desired positions in,on, and around the target tissue 12 to receive treatment as describedherein. Similarly, sensors S1, S2 are implanted in the patient 14 in,on, or around the target tissue 12 either coincident with or inproximity to the electrodes 30. One or more leads 18 extending from theelectrodes 30 and the sensors S1, S2 can be connected to an electricalsignal generator 40, controller 50, external controller 60, and/orexternal user interface 62. Typically, but not necessarily, theelectrical signal generator 40 will be external to the patient 14 whilethe example embodiment of the neuromodulation system 10 is being set upfor permanent implantation in the patient 14 or if the system is beingset up to provide only temporary treatment. Once the setup is completed,the implantable electrical signal generator 40 typically will bepermanently implanted in the patient 14 in the implantable enclosure 16.

A user or operator may use the user interface 62 and the controller 50or external controller 60 to select an electrode 30 or combination ofelectrodes 30, cause the electrical signal generator 40 to selectivelygenerate and deliver electrical noise stimulation signals to the targettissue 12, and monitor the sensor data produced by the sensors S1, S2 asdescribed herein. The controller 50 or external controller 60 controlsthe electrical signal generator 40 as described herein to scan or sweepthe center frequency of a relatively narrow band of electrical noisestimulation signals across the entire bandwidth or a portion of thebandwidth of possible frequencies for such signals and determines aplurality of peak values of impedance present at a plurality ofdifferent center frequencies. The process is repeated for a plurality ofdifferent selected electrodes 30 and/or combinations of electrodes 30 asdesired.

If necessary or desired, one or more of the electrodes 30 and sensorsS1, S2 can be repositioned, for example to provide better contact, alterthe distance and/or orientation of the electrodes 30 and/or sensors S1,S2 relative to the target tissue 12, better position the electrodes 30in specific neural and/or non-neural tissue of the target tissue 12 etc.in order to achieve better peak values of the impedance. The process todetermine the peak values of impedance in relation to frequency can thenbe repeated. One or more of the electrodes 30 and sensors S1, S2 can berepositioned and the process to determine the peak values of impedancecan be repeated as many times as necessary in order to obtain one ormore sets or pluralities of peak values of impedance that aresatisfactory for use in providing treatment.

The user or operator then uses the user interface 62 and the controller50 or external controller 60 to generate and deliver electrical noisestimulation signals to the target tissue 12 of the patient 14 tostimulate or modulate the target tissue 12 and provide treatment for oneor more conditions, including one or more of the conditions identifiedherein. The electrical noise stimulation signals are generated anddelivered to the target tissue 12 in the manner described herein tooptimize and maximize the electric field in the target tissue 12 bymaximizing the voltage while maintaining an acceptably low level ofcurrent density to provide an optimal therapeutic result while alsopreventing overheating and damage to the target tissue 12 and discomfortto the patient 14.

Once the desired therapeutic results are achieved, the leads 18 can beconnected to the lead connection ports 19 of the implantable enclosure16 to electrically couple the electrodes 30 and sensors S1, S2 to theimplantable controller 50 and the implantable electrical signalgenerator 40 within the implantable enclosure 16. The implantableenclosure 16 is then implanted in the patient permanently inconventional fashion.

Thereafter, the patient 14 or a user or operator of the exampleembodiment of the neuromodulation system 10 can use the externalcontroller 60 if included or another remote device to periodicallycommunicate with the implantable controller 50 and manually initiate atreatment dose when needed. The treatment dose can have a presetduration and/or preset parameters for the electrical noise stimulationsignals, such as peak voltage level. Alternatively, the duration andsome or all parameters of the electrical noise stimulation signals canbe manually selected by the patient 14 or a user or operator. Alsoalternatively, the implantable controller 50 can be configured toautomatically initiate treatment doses on a predetermined schedule andwith predetermined duration and preset parameters of the electricalnoise stimulation signals.

Any and all headings are for convenience only and have no limitingeffect. Unless otherwise defined, all technical and scientific termsused herein have the same meaning as commonly understood by one ofordinary skill in the art to which this invention belongs. Althoughspecific terms are employed herein, they are used in a generic anddescriptive sense only and not for purposes of limitation. Allpublications, patent applications, patents, and other referencesmentioned herein are incorporated by reference in their entirety to theextent allowed by applicable law and regulations.

Any data structures and code described in this detailed description aretypically stored on a computer readable storage medium, which may be anydevice or medium that can store code and/or data for use by a computersystem. This includes, but is not limited to, magnetic and opticalstorage devices such as disk drives, magnetic tape, CDs (compact discs),DVDs (digital video discs), and computer instruction signals embodied ina transmission medium (with or without a carrier wave upon which thesignals are modulated). For example, the transmission medium may includea telecommunications network, such as the Internet.

At least one embodiment of the neuromodulation system and method withfeedback optimized electrical field generation is described above withreference to block and/or flow diagrams of systems, methods,apparatuses, and/or computer program products according to exampleembodiments of the invention. It will be understood that one or moreblocks of the block diagrams and flow diagrams, and combinations ofblocks in the block diagrams and flow diagrams, respectively, can beimplemented by computer-executable program instructions. Likewise, someblocks of the block diagrams and flow diagrams may not necessarily needto be performed in the order presented, or may not necessarily need tobe performed at all, according to some embodiments of the invention.These computer-executable program instructions may be loaded onto ageneral-purpose computer, a special-purpose computer, a processor, orother programmable data processing apparatus to produce a particularmachine, such that the instructions that execute on the computer,processor, or other programmable data processing apparatus create meansfor implementing one or more functions specified in the flow diagramblock or blocks. These computer program instructions may also be storedin a computer-readable memory that can direct a computer or otherprogrammable data processing apparatus to function in a particularmanner, such that the instructions stored in the computer-readablememory produce an article of manufacture including instruction meansthat implement one or more functions specified in the flow diagram blockor blocks. As an example, embodiments of the invention may provide for acomputer program product, comprising a computer usable medium having acomputer-readable program code or program instructions embodied therein,the computer-readable program code adapted to be executed to implementone or more functions specified in the flow diagram block or blocks. Thecomputer program instructions may also be loaded onto a computer orother programmable data processing apparatus to cause a series ofoperational elements or steps to be performed on the computer or otherprogrammable apparatus to produce a computer-implemented process suchthat the instructions that execute on the computer or other programmableapparatus provide elements or steps for implementing the functionsspecified in the flow diagram block or blocks. Accordingly, blocks ofthe block diagrams and/or flow diagrams support combinations of meansfor performing the specified functions, combinations of elements orsteps for performing the specified functions, and program instructionmeans for performing the specified functions. It will also be understoodthat each block of the block diagrams and/or flow diagrams, andcombinations of blocks in the block diagrams and/or flow diagrams, canbe implemented by special-purpose, hardware-based computer systems thatperform the specified functions, elements or steps, or combinations ofspecial-purpose hardware and computer instructions.

The present invention may be embodied in other specific forms withoutdeparting from the spirit or essential attributes thereof, and it istherefore desired that the present embodiment be considered in allrespects as illustrative and not restrictive. Many modifications andother embodiments of the neuromodulation system and method with feedbackoptimized electrical field generation will come to mind to one skilledin the art to which this invention pertains and having the benefit ofthe teachings presented in the foregoing description and the associateddrawings. Further, features illustrated or described as part of oneembodiment may be used on another embodiment to yield a still furtherembodiment. Therefore, it is to be understood that the invention is notto be limited to the specific embodiments disclosed and thatmodifications and other embodiments are intended to be included withinthe scope of the appended claims. Although methods and materials similarto or equivalent to those described herein can be used in the practiceor testing of the neuromodulation system and method with feedbackoptimized electrical field generation, suitable methods and materialsare described above. Thus, the neuromodulation system and method withfeedback optimized electrical field generation is not intended to belimited to the embodiments shown, but is to be accorded the widest scopeconsistent with the principles and features disclosed herein.

What is claimed is:
 1. A system, comprising: an electrical signalgenerator adapted to generate an electrical noise stimulation signal; animplantable electrode adapted to receive the electrical noisestimulation signal and to produce an electric field for application to atarget tissue; a temperature sensor adapted to be implantable in or nearthe target tissue, wherein the temperature sensor is configured togenerate a temperature data indicative of a temperature associated withthe target tissue in response to application of the electric field tothe target tissue; a controller in communication with the electricalsignal generator and the temperature sensor, wherein the controller isconfigured to: receive the temperature data; and automatically controlthe electrical signal generator in response to the temperature data togenerate the electrical noise stimulation signal to optimize theelectric field to produce a therapeutic effect without the temperaturedata indicating potential damage to the target tissue by the electricalnoise stimulation signal.
 2. The system of claim 1, wherein theelectrical signal generator is adapted to be implantable.
 3. The systemof claim 1, wherein the controller is configured to respond to thetemperature data indicating the temperature is associated with potentialdamage to the target tissue by automatically reducing a strength of theelectric field.
 4. The system of claim 3, wherein the controller isconfigured to respond to the temperature data indicating the temperatureis associated with potential damage to the target tissue byautomatically reducing a current density or a current flow of theelectric field.
 5. The system of claim 1, wherein the controller isconfigured to control the electrical signal generator to limit a dose ofthe electric field to produce the therapeutic effect.
 6. The system ofclaim 1, wherein the controller is configured to control the electricalsignal generator to optimize the electric field by maximizing a voltageof the electric field.
 7. The system of claim 1, wherein the controlleris configured to receive input about patient sensations in response toapplication of the electric field to the target tissue, and to controlthe electrical signal generator in response to the input about patientsensations to adjust the electric field.
 8. The system of claim 1,wherein the therapeutic effect is for treating at least one condition ina group of conditions comprising chronic pain, acute pain, autonomicdisorder, sensory disorder, motor disorder, and cognitive disorder. 9.The system of claim 1, wherein the therapeutic effect is for treating achronic pain condition or an acute pain condition.
 10. The system ofclaim 1, wherein the therapeutic effect comprises a plastic long-termfunctional change in the target tissue to lessen or eliminate apathophysiologic disease or syndrome.
 11. The system of claim 1, whereinthe target tissue comprises at least one tissue that is within oradjacent to a tissue in a group comprising brain, spinal cord, dorsalroot ganglion, sympathetic chain ganglion, cranial nerve,parasympathetic nerve, and peripheral nerve.
 12. The system of claim 1,wherein the target tissue comprises tissue that is within or adjacent toa peripheral nerve comprising at least one of a tibial nerve, a sacralnerve, a sacral nerve plexus, a sacral foramen, and a sciatic nerve. 13.The system of claim 1, wherein the target tissue comprises a neuraltissue.
 14. The system of claim 1, wherein the electrical noisestimulation signal comprises at least one form of noise in a groupcomprising Gaussian noise, white noise, pink noise, Brownian noise, rednoise, and grey noise.
 15. The system of claim 1, wherein the electricalnoise stimulation signal has a peak voltage level in the range of about5V to about 200V and a frequency spectrum in the range of about 100 Hz.to about 750 KHz.
 16. A method of using the system of claim 1,comprising: implanting the implantable electrode into or near the targettissue of a patient; implanting the temperature sensor into or near thetarget tissue of the patient; applying the electric field from theimplantable electrode to the target tissue; generating the temperaturedata by the temperature sensor; and automatically controlling theelectrical signal generator by the controller in response to thetemperature data to generate the electrical noise stimulation signal tooptimize the electric field to produce the therapeutic effect withoutthe temperature data indicating potential damage to the target tissue bythe electrical noise stimulation signal.
 17. The method of claim 16,wherein the step of automatically controlling the electrical signalgenerator comprises reducing a current density or a current flow to thetarget tissue if the temperature data indicates potential damage to thetarget tissue.
 18. The method of claim 16, wherein the step ofautomatically controlling the electrical signal generator comprisesreducing a strength of the electric field if the temperature dataindicates potential damage to the target tissue.
 19. The method of claim16, wherein the step of automatically controlling the electrical signalgenerator comprises limiting a dose of the electric field if thetemperature data indicates potential damage to the target tissue. 20.The method of claim 16, wherein the step of automatically controllingthe electrical signal generator comprises controlling the electric fieldto maximize a voltage of the electric field.
 21. The method of claim 16,including the step of receiving input about sensations of the patient inresponse to application of the electric field to the target tissue. 22.A system, comprising: an electrical signal generator adapted to generatean electrical noise stimulation signal; an implantable electrode adaptedto be implanted into or near a target tissue, wherein the implantableelectrode is adapted to receive the electrical noise stimulation signaland to produce an electric field for application to the target tissue; atemperature sensor adapted to be implanted in or near the target tissue,wherein the temperature sensor is configured to generate a temperaturedata indicative of a temperature associated with the target tissue inresponse to application of the electric field to the target tissue; anda controller in communication with the electrical signal generator andthe temperature sensor, wherein the controller is configured to: receivethe temperature data; and automatically control the electrical signalgenerator in response to the temperature data to generate the electricalnoise stimulation signal to maximize a voltage of the electric field toproduce a therapeutic effect without the temperature data indicatingpotential damage to the target tissue by the electrical noisestimulation signal.
 23. The system of claim 22, wherein the electricalsignal generator is adapted to be implantable.
 24. The system of claim22, wherein the controller is configured to respond to the temperaturedata indicating the temperature is associated with potential damage tothe target tissue by automatically reducing the voltage of the electricfield.
 25. The system of claim 22, wherein the controller is configuredto control the electrical signal generator to limit a dose of theelectric field to produce the therapeutic effect.
 26. The system ofclaim 22, wherein the controller is configured to receive input aboutpatient sensations in response to application of the electric field tothe target tissue, and to control the electrical signal generator inresponse to the input about patient sensations to adjust the electricfield.
 27. The system of claim 22, wherein the therapeutic effect is fortreating at least one condition in a group of conditions comprisingchronic pain, acute pain, autonomic disorder, sensory disorder, motordisorder, and cognitive disorder.
 28. The system of claim 22, whereinthe therapeutic effect is for treating a chronic pain condition or anacute pain condition.
 29. The system of claim 22, wherein thetherapeutic effect comprises a plastic long-term functional change inthe target tissue to lessen or eliminate a pathophysiologic disease orsyndrome.
 30. The system of claim 22, wherein the target tissuecomprises at least one tissue that is within or adjacent to a tissue ina group comprising brain, spinal cord, dorsal root ganglion, sympatheticchain ganglion, cranial nerve, parasympathetic nerve, and peripheralnerve.
 31. The system of claim 22, wherein the target tissue comprisestissue that is within or adjacent to a peripheral nerve comprising atleast one of a tibial nerve, a sacral nerve, a sacral nerve plexus, asacral foramen, and a sciatic nerve.
 32. The system of claim 22, whereinthe target tissue comprises a neural tissue.
 33. The system of claim 22,wherein the electrical noise stimulation signal comprises at least oneform of noise in a group comprising Gaussian noise, white noise, pinknoise, Brownian noise, red noise, and grey noise.
 34. The system ofclaim 22, wherein the electrical noise stimulation signal has a peakvoltage level in the range of about 5V to about 200V and a frequencyspectrum in the range of about 100 Hz. to about 750 KHz.
 35. A method ofusing the system of claim 22, comprising: implanting the implantableelectrode into or near the target tissue of a patient; implanting thetemperature sensor into or near the target tissue of the patient;applying the electric field from the implantable electrode to the targettissue; generating the temperature data by the temperature sensor; andautomatically controlling the electrical signal generator by thecontroller in response to the temperature data to generate theelectrical noise stimulation signal to optimize the electric field toproduce the therapeutic effect without the temperature data indicatingpotential damage to the target tissue by the electrical noisestimulation signal.
 36. The method of claim 35, wherein the step ofautomatically controlling the electrical signal generator comprisesreducing a current density or a current flow to the target tissue if thetemperature data indicates potential damage to the target tissue. 37.The method of claim 35, wherein the step of automatically controllingthe electrical signal generator comprises reducing a strength of theelectric field if the temperature data indicates potential damage to thetarget tissue.
 38. The method of claim 35, wherein the step ofautomatically controlling the electrical signal generator compriseslimiting a dose of the electric field if the temperature data indicatespotential damage to the target tissue.
 39. The method of claim 35,wherein the step of automatically controlling the electrical signalgenerator comprises controlling the electric field to maximize a voltageof the electric field.
 40. The method of claim 35, including the step ofreceiving input about sensations of the patient in response toapplication of the electric field to the target tissue.
 41. A system,comprising: an electrical signal generator adapted to generate anelectrical noise stimulation signal; an implantable electrode adapted tobe implanted into or near a target tissue, wherein the implantableelectrode is adapted to receive the electrical noise stimulation signalfrom the electrical signal generator and to produce an electric fieldfor application to the target tissue; a temperature sensor adapted to beimplanted in or near the target tissue, wherein the temperature sensoris configured to generate a temperature data indicative of a temperatureassociated with the target tissue in response to application of theelectric field to the target tissue; and a controller in communicationwith the electrical signal generator and the temperature sensor, whereinthe controller is configured to: receive the temperature data; andautomatically control the electrical signal generator to reduce astrength of the electric field in response to wherein the temperaturedata indicates the temperature associated with the target tissue isassociated with potential damage to the target tissue.
 42. The system ofclaim 41, wherein the electrical signal generator is adapted to beimplantable.
 43. The system of claim 41, wherein the controller isconfigured to respond to the temperature data indicating the temperatureis associated with potential damage to the target tissue byautomatically reducing a voltage of the electric field.
 44. The systemof claim 41, wherein the controller is configured to control theelectrical signal generator to limit a dose of the electric field toproduce a therapeutic effect.
 45. The system of claim 41, wherein thecontroller is configured to receive input about patient sensations inresponse to application of the electric field to the target tissue, andto control the electrical signal generator in response to the inputabout patient sensations to adjust the electric field.
 46. The system ofclaim 41, wherein the target tissue comprises at least one tissue thatis within or adjacent to a tissue in a group comprising brain, spinalcord, dorsal root ganglion, sympathetic chain ganglion, cranial nerve,parasympathetic nerve, and peripheral nerve.
 47. The system of claim 41,wherein the target tissue comprises tissue that is within or adjacent toa peripheral nerve comprising at least one of a tibial nerve, a sacralnerve, a sacral nerve plexus, a sacral foramen, and a sciatic nerve. 48.The system of claim 41, wherein the target tissue comprises a neuraltissue.
 49. The system of claim 41, wherein the electrical noisestimulation signal comprises at least one form of noise in a groupcomprising Gaussian noise, white noise, pink noise, Brownian noise, rednoise, and grey noise.
 50. The system of claim 41, wherein theelectrical noise stimulation signal has a peak voltage level in therange of about 5V to about 200V and a frequency spectrum in the range ofabout 100 Hz. to about 750 KHz.
 51. A method of using the system ofclaim 41, comprising: implanting the implantable electrode into or nearthe target tissue of a patient; implanting the temperature sensor intoor near the target tissue of the patient; applying the electric fieldfrom the implantable electrode to the target tissue; generating thetemperature data by the temperature sensor; and automaticallycontrolling the electrical signal generator by the controller inresponse to the temperature data to generate the electrical noisestimulation signal to optimize the electric field without thetemperature data indicating potential damage to the target tissue by theelectrical noise stimulation signal.
 52. The method of claim 51, whereinthe step of automatically controlling the electrical signal generatorcomprises reducing a current density or a current flow to the targettissue if the temperature data indicates potential damage to the targettissue.
 53. The method of claim 51, wherein the step of automaticallycontrolling the electrical signal generator comprises reducing astrength of the electric field if the temperature data indicatespotential damage to the target tissue.
 54. The method of claim 51,wherein the step of automatically controlling the electrical signalgenerator comprises limiting a dose of the electric field if thetemperature data indicates potential damage to the target tissue. 55.The method of claim 51, wherein the step of automatically controllingthe electrical signal generator comprises controlling the electric fieldto maximize a voltage of the electric field.
 56. The method of claim 51,including the step of receiving input about sensations of the patient inresponse to application of the electric field to the target tissue.